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Sample records for cascade chemokine il-8

  1. Human monocyte-derived dendritic cells expressing both chemotactic cytokines IL-8, MCP-1, RANTES and their receptors,and their selective migration to these chemokines

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To characterize the mRNA expression of CXC chemokine IL-8, CC chemokine monocyte chemothractant protein-1 (MCP-1) and regulated on activation,normal T cell expressed and secreted (RANTES), and a newly defined DC chemokine DC- CK1 as well as the expression of IL-8 receptor, MCP-1 receptor and RANTES receptor in human monocyte derived dendritic cells (MoDCs).The migratory responsiveness of MoDC to IL-8, MCP-1 and RANTES was alsso studied. Methods In vitro generated MoDCs were obtained by differentiating monocytes in the presence of GM-CSF and IL-4 for 5 days. The time course of RNA expression was analyzed by RT-PCR and migratoly ability was assessed by a micromultiwell chemotaxis chamber assay. Results IL-8, MCP-1, RANTES and their corres ponding receptors were consistently expressed in MoDCs. DC-CK-1 expression was detectable efter 48 hours of differentiation. MoDC selectively migrated in response to MCP-1 and RANTES but not to IL-8 though transcripts of IL-8 receptor were present. Conclusion Because the capacity of dendritic cells to initiate immune responses depends on their specialized migratory and tissue homing properties, the expression of chemokines and their receptors along with the migratory responsiveness to chemokines of MoDC in our study suggests a potential role of chemokines in the interaction between dendritic cells and T cells and the induction of immune responses.

  2. A surface membrane protein of Entamoeba histolytica functions as a receptor for human chemokine IL-8: its role in the attraction of trophozoites to inflammation sites.

    Science.gov (United States)

    Diaz-Valencia, J Daniel; Pérez-Yépez, Eloy Andrés; Ayala-Sumuano, Jorge Tonatiuh; Franco, Elizabeth; Meza, Isaura

    2015-12-01

    Entamoeba histolytica trophozoites respond to the presence of IL-8, moving by chemotaxis towards the source of the chemokine. IL-8 binds to the trophozoite membrane and triggers a response that activates signaling pathways that in turn regulate actin/myosin cytoskeleton organisation to initiate migration towards the chemokine, suggesting the presence of a receptor for IL-8 in the parasite. Antibodies directed to the human IL-8 receptor (CXCR1) specifically recognised a 29 kDa protein in trophozoite membrane fractions. The same protein was immunoprecipitated by this antibody from total amebic extracts. Peptide analysis of the immunoprecipitated protein revealed a sequence with high homology to a previously identified amebic outer membrane peroxiredoxin and a motif within the third loop of human CXCR1, which is an important site for IL-8 binding and activation of signaling processes. Immunodetection assays demonstrated that the anti-human CXCR1 antibody binds to the 29 kDa protein in a different but close site to where IL-8 binds to the trophozoite surface membrane, suggesting that human and amebic receptors for this chemokine share common epitopes. In the context of the human intestinal environment, a receptor for IL-8 could be a great advantage for E. histolytica trophozoite survival, as they could reach an inflammatory milieu containing abundant nutrients. In addition, it has been suggested that the high content of accessible thiol groups of the protein and its peroxidase activity could provide protection in the oxygen rich milieu of colonic lesions, allowing trophozoite invasion of other tissues and escape from the host immune response.

  3. Solution NMR characterization of chemokine CXCL8/IL-8 monomer and dimer binding to glycosaminoglycans: structural plasticity mediates differential binding interactions.

    Science.gov (United States)

    Joseph, Prem Raj B; Mosier, Philip D; Desai, Umesh R; Rajarathnam, Krishna

    2015-11-15

    Chemokine CXCL8/interleukin-8 (IL-8) plays a crucial role in directing neutrophils and oligodendrocytes to combat infection/injury and tumour cells in metastasis development. CXCL8 exists as monomers and dimers and interaction of both forms with glycosaminoglycans (GAGs) mediate these diverse cellular processes. However, very little is known regarding the structural basis underlying CXCL8-GAG interactions. There are conflicting reports on the affinities, geometry and whether the monomer or dimer is the high-affinity GAG ligand. To resolve these issues, we characterized the binding of a series of heparin-derived oligosaccharides [heparin disaccharide (dp2), heparin tetrasaccharide (dp4), heparin octasaccharide (dp8) and heparin 14-mer (dp14)] to the wild-type (WT) dimer and a designed monomer using solution NMR spectroscopy. The pattern and extent of binding-induced chemical shift perturbation (CSP) varied between dimer and monomer and between longer and shorter oligosaccharides. NMR-based structural models show that different interaction modes coexist and that the nature of interactions varied between monomer and dimer and oligosaccharide length. MD simulations indicate that the binding interface is structurally plastic and provided residue-specific details of the dynamic nature of the binding interface. Binding studies carried out under conditions at which WT CXCL8 exists as monomers and dimers provide unambiguous evidence that the dimer is the high-affinity GAG ligand. Together, our data indicate that a set of core residues function as the major recognition/binding site, a set of peripheral residues define the various binding geometries and that the structural plasticity of the binding interface allows multiplicity of binding interactions. We conclude that structural plasticity most probably regulates in vivo CXCL8 monomer/dimer-GAG interactions and function.

  4. IL-8 as antibody therapeutic target in inflammatory diseases

    DEFF Research Database (Denmark)

    Skov, Lone; Beurskens, Frank J; Zachariae, Claus O C;

    2008-01-01

    IL-8 is a chemokine that has been implicated in a number of inflammatory diseases involving neutrophil activation. HuMab 10F8 is a novel fully human mAb against IL-8, which binds a discontinuous epitope on IL-8 overlapping the receptor binding site, and which effectively neutralizes IL-8-dependen...

  5. Chemokines

    Directory of Open Access Journals (Sweden)

    Richard Horuk

    2007-01-01

    Full Text Available Chemokines are a family of polypeptides that direct the migration of leukocytestoward a site of infection. They play a major role in autoimmune disease and chemokine receptors have recently been found to mediate HIV-1 fusion. In this short review we examine the role of chemokines in host defence and in the pathophysiology of autoimmune diseases. We conclude by discussing various therapeutic approaches that target chemokine receptors and that could be beneficial in disease.

  6. Nebulized hypertonic saline decreases IL-8 in sputum of patients with cystic fibrosis.

    LENUS (Irish Health Repository)

    Reeves, Emer P

    2011-06-01

    Inflammation within the cystic fibrosis (CF) lung is mediated by inflammatory chemokines, such as IL-8. IL-8 is protected from proteolytic degradation in the airways by binding to glycosaminoglycans, while remaining active. Evidence that increased hypertonicity of airway secretions induced by hypertonic saline treatment alters levels of IL-8 is lacking.

  7. Nebulized hypertonic saline decreases IL-8 in sputum of patients with cystic fibrosis.

    LENUS (Irish Health Repository)

    Reeves, Emer P

    2012-02-01

    RATIONALE: Inflammation within the cystic fibrosis (CF) lung is mediated by inflammatory chemokines, such as IL-8. IL-8 is protected from proteolytic degradation in the airways by binding to glycosaminoglycans, while remaining active. Evidence that increased hypertonicity of airway secretions induced by hypertonic saline treatment alters levels of IL-8 is lacking. OBJECTIVES: To investigate the antiinflammatory effect of hypertonic saline (HTS) treatment within the CF lung by focusing on IL-8. METHODS: Degradation of IL-8 in CF lung secretions after treatment with glycosaminoglycan lyases and HTS was analyzed by Western blot analysis and ELISA. The ex vivo chemotactic activity of purified neutrophils in response to CF airway secretions was evaluated post nebulization of HTS (7% saline). MEASUREMENTS AND MAIN RESULTS: In vivo CF bronchoalveolar lavage fluid (BALF) IL-8 levels were significantly higher than the control group (P < 0.05). Digesting glycosaminoglycans in CF BALF displaced IL-8 from glycosaminoglycan matrices, rendering the chemokine susceptible to proteolytic cleavage. High sodium concentrations also liberate IL-8 in CF BALF in vitro, and in vivo in CF sputum from patients receiving aerosolized HTS, resulting in degradation of IL-8 and decreased neutrophil chemotactic efficiency. CONCLUSIONS: Glycosaminoglycans possess the ability to influence the chemokine profile of the CF lung by binding and stabilizing IL-8, which promotes neutrophil chemotaxis and activation. Nebulized hypertonic saline treatment disrupts the interaction between glycosaminoglycans and IL-8, rendering IL-8 susceptible to proteolytic degradation with subsequent decrease in neutrophil chemotaxis, thereby facilitating resolution of inflammation.

  8. ERβ and PEA3 co-activate IL-8 expression and promote the invasion of breast cancer cells.

    Science.gov (United States)

    Chen, Ying; Chen, Li; Li, Ji-Yu; Mukaida, Naofumi; Wang, Qiaoqiao; Yang, Chen; Yin, Wen-Jin; Zeng, Xiao-Hua; Jin, Wei; Shao, Zhi-ming

    2011-03-01

    Metastasis represents the major remaining cause of mortality in human breast cancer. Interleukin-8 (IL-8), a proinflammatory chemokine, plays an important role during tumor angiogenesis and metastasis. In this study, we found that IL-8 and ERβ showed positive association. Overexpression of ERβ or PEA3 could up-regulate IL-8 promoter activity, mRNA and secretion; silencing of ERβ or PEA3 decreased IL-8 mRNA and secretion. ERβ and PEA3 increased IL-8 expression through binding to the IL-8 promoter and increased cell invasion. HER2 could increase ERβ and PEA3 expression and their binding to the IL-8 promoter. We conclude that ERβ and PEA3 play important roles in tumor invasion by regulating IL-8 expression, and HER2 maybe the upstream of ERβ and PEA3 - IL-8 pathway.

  9. Regulation of CXCL8/IL-8 expression by zonula occludens-1 in human breast cancer cells.

    Science.gov (United States)

    Brysse, Anne; Mestdagt, Mélanie; Polette, Myriam; Luczka, Emilie; Hunziker, Walter; Noël, Agnès; Birembaut, Philippe; Foidart, Jean-Michel; Gilles, Christine

    2012-01-01

    Accumulating data now suggest that ZO-1, once delocalized from tight junctions, could be implicated in the regulation of tumor-promoting genes. Because of their major implication in different steps of tumor progression, we investigated here the influence of ZO-1 on chemokines expression in breast cancer cells. Using GeneArray analysis to compare chemokine mRNA expression in breast tumor cells transfected with a siRNA against ZO-1, we identified CXCL-8IL-8 as a major potential target of ZO-1 signaling, being strongly downregulated following ZO-1 siRNA transfection. Examining further the relationship between ZO-1 and interleukin-8 (CXCL8/IL-8), we first showed that CXCL8/IL-8 expression correlates with a relocalization of ZO-1 in several breast cancer cell lines. Moreover, CXCL8/IL-8 is downregulated in invasive BT549 cells transfected with three different ZO-1 siRNA and overexpressed in noninvasive BT20 and SKBR3 cells transfected with vectors expressing ZO-1. We also provide evidence for an activation of the CXCL8/IL-8 promoter by ZO-1. Finally, we show that the regulation of CXCL8/IL-8 by ZO-1 is independent of the β-catenin pathway. Our results thus clearly show an implication of ZO-1 in CXCL8/IL-8 regulation. Because of the major implications of CXCL8/IL-8 in tumor invasion, such a regulation could play an important role in breast cancer progression.

  10. ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion.

    Science.gov (United States)

    Chen, Wei-Ta; Ebelt, Nancy D; Stracker, Travis H; Xhemalce, Blerta; Van Den Berg, Carla L; Miller, Kyle M

    2015-06-01

    Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse xenograft model and clinical data validated IL-8 in lung metastasis. These findings provide insights into how ATM activation by oxidative stress regulates IL-8 to sustain cell migration and invasion in cancer cells to promote metastatic potential. Thus, in addition to well-established roles in tumor suppression, these findings identify a role for ATM in tumor progression.

  11. Fulminant lymphocytic choriomeningitis virus-induced inflammation of the CNS involves a cytokine-chemokine-cytokine-chemokine cascade

    DEFF Research Database (Denmark)

    Christensen, Jeanette Erbo; Simonsen, Stine; Fenger, Christina;

    2009-01-01

    Intracerebral inoculation of immunocompetent mice with lymphocytic choriomeningitis virus (LCMV) normally results in fatal CD8+ T cell mediated meningoencephalitis. However, in CXCL10-deficient mice, the virus-induced CD8+ T cell accumulation in the neural parenchyma is impaired, and only 30......-50% of the mice succumb to the infection. Similar results are obtained in mice deficient in the matching chemokine receptor, CXCR3. Together, these findings point to a key role for CXCL10 in regulating the severity of the LCMV-induced inflammatory process. For this reason, we now address the mechanisms regulating...... the expression of CXCL10 in the CNS of LCMV-infected mice. Using mice deficient in type I IFN receptor, type II IFN receptor, or type II IFN, as well as bone marrow chimeras expressing CXCL10 only in resident cells or only in bone marrow-derived cells, we analyzed the up-stream regulation as well as the cellular...

  12. Diesel Exhaust Particles Upregulate Interleukins IL-6 and IL-8 in Nasal Fibroblasts

    Science.gov (United States)

    Park, Il-Ho; Shin, Jae-Min; Lee, Seoung-Ae; Lee, Heung-Man

    2016-01-01

    Background Diesel exhaust particles (DEP) are a major source of air pollution. Nasal fibroblasts are known to produce various cytokines and chemokines. The aim of this study was to evaluate DEP-induced cytokines and chemokines in nasal fibroblasts and to identify the signaling pathway involved. Methods A cytokine and chemokine array performed after stimulation of nasal fibroblasts with DEP revealed that levels of IL-6 and IL-8 were increased most significantly among various cytokines and chemokines. RT—PCR and ELISA were used to determine the mRNA and protein expression levels of IL-6 and IL-8. Signaling pathways of p-38, Akt, and NF-κB were analyzed by western blotting, luciferase assay, and ELISA. Organ cultures of nasal interior turbinate were also developed to demonstrate the ex vivo effect of DEP on the expression of IL-6 and IL-8 and the associated signaling pathway. Results DEP increased the expressions of IL-6 and IL-8 in nasal fibroblasts at mRNA and protein levels. DEP induced phosphorylation of p38, Akt, and NF-κB, whereas inhibitors of p38, Akt, and NF-κB blocked these phophorylations and the expressions of IL-6 and IL-8. These findings were also observed in ex vivo organ culture of nasal inferior turbinate. Conclusions DEP induces expression of IL-6 and IL-8 via p38, Akt, and NF-κB signaling pathways in nasal fibroblasts. This finding suggests that air pollution might induce or aggravate allergic rhinitis or chronic rhinosinusitis. PMID:27295300

  13. Characterization of buffalo interleukin 8 (IL-8 and its expression in endometritis

    Directory of Open Access Journals (Sweden)

    Ahlam A. Abou Mossallam

    2015-06-01

    Full Text Available River buffalo (Bubalus bubalis bubalis with a population over 135 million heads is an important livestock. Interleukin 8 (IL-8 is a member of the chemokine family and is an important chemoattractant for neutrophils associated with a wide variety of inflammatory diseases such as endometritis. Tissue samples from the mammary gland, uterus and ovary were obtained from river buffalo (Mediterranean type with and without endometritis. Bacteriological examination showed the presence of both gram positive and negative in all buffalo with endometritis. RNA extraction and complementary DNA (cDNA synthesis were conducted from all tissues. Specific primer for IL8 full coding regions was designed using known cDNA sequences of Bubalus bubalis, Genbank accession number AY952930.1. IL-8 gene expression was investigated in buffalo tissues. Expression of IL-8 in buffalo with endometritis was found to increase significantly over buffalo without endometritis only in the uterus (P = 0.0159. PCR products from uterus tissues (target organs of buffalo with and without endometritis, were purified and sequenced. No polymorphic sites were detected in the investigated samples. IL-8 cDNA nucleotide sequences of buffalo with and without endometritis were 100% identical (accession number JX413057. Buffalo IL8 cDNAs were compared with corresponding sequences of member of subfamily Bovinae (buffalo and cattle and subfamily Caprinae (sheep and goat. IL-8 species specific differences were identified.

  14. Identification and Expression Profiles of IL-8 in Bighead Carp (Aristichthys nobilis) in Response to Microcystin-LR

    OpenAIRE

    Li, Huiying; Cai, Yan; Xie, Ping; Li, Guangyu; Hao, Le; Xiong, Qian

    2013-01-01

    Microcystin-LR (MCLR) is a widespread cyanotoxin and has immunotoxicity to animals, including fish. Chemokines are considered to play important roles in inflammatory response induced by MCLR. In this study, we cloned the full-length cDNA of interleukin-8 (IL-8) from bighead carp (Aristichthys nobilis) for the first time. The full-length IL-8 cDNA was 552 bp and contained a 297-bp open-reading frame that encoded for a 98-amino acid protein. The deduced IL-8 protein had a typical aspartic acid ...

  15. Interleukin (IL)-8 immunoreactivity of injured axons and surrounding oligodendrocytes in traumatic head injury.

    Science.gov (United States)

    Hayashi, Takahito; Ago, Kazutoshi; Nakamae, Takuma; Higo, Eri; Ogata, Mamoru

    2016-06-01

    Interleukin (IL)-8 has been suggested to be a positive regulator of myelination in the central nervous system, in addition to its principal role as a chemokine for neutrophils. Immunostaining for beta-amyloid precursor protein (AβPP) is an effective tool for detecting traumatic axonal injury, although AβPP immunoreactivity can also indicate axonal injury due to hypoxic causes. In this study, we examined IL-8 and AβPP immunoreactivity in sections of corpus callosum obtained from deceased patients with blunt head injury and from equivalent control tissue. AβPP immunoreactivity was detected in injured axons, such as axonal bulbs and varicose axons, in 24 of 44 head injury cases. These AβPP immunoreactive cases had survived for more than 3h. The AβPP immunostaining pattern can be classified into two types: traumatic (Pattern 1) and non-traumatic (Pattern 2) axonal injuries, which we described previously [Hayashi et al. Int. J. Legal Med. 129 (2015) 1085-1090]. Three of 44 control cases also showed AβPP immunoreactive injured axons as Pattern 2. In contrast, IL-8 immunoreactivity was detected in 7 AβPP immunoreactive and in 2 non-AβPP immunoreactive head injury cases, but was not detected in any of the 44 control cases, including the 3 AβPP immunoreactive control cases. The IL-8 immunoreactive cases had survived from 3 to 24 days, whereas those cases who survived less than 3 days (n=29) and who survived 90 days (n=1) were not IL-8 immunoreactive. Moreover, IL-8 was detected as Pattern 1 axons only. In addition, double immunofluorescence analysis showed that IL-8 is expressed by oligodendrocytes surrounding injured axons. In conclusion, our results suggest that immunohistochemical detection of IL-8 may be useful as a complementary diagnostic marker of traumatic axonal injury.

  16. Combined effects of IL-8 and CXCR2 gene polymorphisms on breast cancer susceptibility and aggressiveness

    Directory of Open Access Journals (Sweden)

    Helal Ahmed N

    2010-06-01

    Full Text Available Abstract Background Interleukin-8 (IL-8/CXCL-8 is a prototype of the ELR+CXC chemokines that play an important role in the promotion and progression of many human cancers including breast cancer. We have recently showed the implication of polymorphism (-251 T/A of IL-8 gene in the susceptibility and prognosis of breast carcinoma. IL-8 acts through its CXCR1 and CXCR2 receptors. CXCR2, expressed on the endothelial cells, is the receptor involved in mediating the angiogenic effects of ELR+CXC chemokines and in particular IL-8. In the current study, we investigated the susceptibility and prognostic implications of the genetic variation in CXCR2 in breast carcinoma. We also confirmed the implication of IL-8 (-251 T/A polymorphism in a larger cohort. Finally, we combined the IL-8 and CXCR2 variant alleles and analyzed their effects in breast cancer risk and prognosis. Methods We used the allele-specific polymerase chain reaction to characterize the variation of IL-8 and CXCR2 for 409 unrelated Tunisian patients with breast carcinoma and 301 healthy control subjects. To estimate the relative risks, Odds ratios and 95% confidence intervals were calculated using unconditional logistic regression after adjusting for the known risk factors for breast cancer. Associations of the genetic marker with the rates of breast carcinoma-specific overall survival and disease-free survival were assessed using univariate and multivariate analyses. Results A highly significant association was found between the homozygous CXCR2 (+ 1208 TT genotype (adjusted OR = 2.89; P = 0.008 and breast carcinoma. A significantly increased risk of breast carcinoma was associated with IL-8 (-251 A allele (adjusted OR = 1.86; P = 0.001. The presence of two higher risk genotypes (the TA and TT in IL-8, and the TT in CXCR2 significantly increased the risk of developing breast carcinoma (adjusted OR = 4.15; P = 0.0004. The CXCR2 (+ 1208 T allele manifested a significant association with an

  17. Characterization of buffalo interleukin 8 (IL-8) and its expression in endometritis

    OpenAIRE

    Ahlam A. Abou Mossallam; El Nahas, Soheir M; Eman R. Mahfouz; Osman, Noha M

    2015-01-01

    River buffalo (Bubalus bubalis bubalis) with a population over 135 million heads is an important livestock. Interleukin 8 (IL-8) is a member of the chemokine family and is an important chemoattractant for neutrophils associated with a wide variety of inflammatory diseases such as endometritis. Tissue samples from the mammary gland, uterus and ovary were obtained from river buffalo (Mediterranean type) with and without endometritis. Bacteriological examination showed the presence of both gram ...

  18. Identification and expression profiles of IL-8 in bighead carp (Aristichthys nobilis) in response to microcystin-LR.

    Science.gov (United States)

    Li, Huiying; Cai, Yan; Xie, Ping; Li, Guangyu; Hao, Le; Xiong, Qian

    2013-10-01

    Microcystin-LR (MCLR) is a widespread cyanotoxin and has immunotoxicity to animals, including fish. Chemokines are considered to play important roles in inflammatory response induced by MCLR. In this study, we cloned the full-length cDNA of interleukin-8 (IL-8) from bighead carp (Aristichthys nobilis) for the first time. The full-length IL-8 cDNA was 552 bp and contained a 297-bp open-reading frame that encoded for a 98-amino acid protein. The deduced IL-8 protein had a typical aspartic acid (D)-leucine (L)-arginine (R) and a CXC motif at the N-terminal, which were conserved in most fish species. Phylogenetic analysis showed that bighead carp IL-8 protein was grouped in the teleost IL-8 lineage 2. Under normal conditions, the expression of IL-8 is constitutive and weak in all tested tissues. However, MCLR treatment could significantly increase the transcription of IL-8 in bighead carp in a temporal- and dose-dependent pattern. The present study will help us to understand more about the evolution of IL-8 and its function in the MCLR induced proinflammatory response in bighead carp. PMID:23797979

  19. The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma.

    Science.gov (United States)

    Stronach, Euan A; Cunnea, Paula; Turner, Christina; Guney, Tankut; Aiyappa, Radhika; Jeyapalan, Senthuran; de Sousa, Camila H; Browne, Alacoque; Magdy, Nesreen; Studd, James B; Sriraksa, Ruethairat; Gabra, Hani; El-Bahrawy, Mona

    2015-10-13

    Platinum based drugs are the cornerstone of chemotherapy for ovarian cancer, however the development of chemoresistance hinders its success. IL-8 is involved in regulating several pro-survival pathways in cancer. We studied the expression of IL-8 and IL-8 receptors in platinum sensitive and resistant cell lines. Using qRT-PCR and immunohistochemistry, both platinum sensitive (PEA1, PEO14) and resistant (PEA2, PEO23) show increased expression of IL-8 and IL-8 receptors. IL-8RA shows nuclear and cytoplasmic expression, whilst IL-8RB is present solely in the cytoplasm. Knockdown of IL-8 increased sensitivity to cisplatin in platinum sensitive and reversed platinum resistance in resistant cell lines, decreased the expression of anti-apoptotic Bcl-2 and decreased inhibitory phosphorylation of pro-apoptotic Bad. IL-8 receptor antagonist treatment also enhanced platinum sensitivity. Nuclear localisation of IL-8RA was only detected in platinum resistant tumours. Inhibition of IL-8 signalling can enhance response in platinum sensitive and resistant disease. Nuclear IL-8RA may have potential as a biomarker of resistant disease. PMID:26267317

  20. Differential transcriptional regulation of IL-8 expression by human airway epithelial cells exposed to diesel exhaust particles

    International Nuclear Information System (INIS)

    Exposure to diesel exhaust particles (DEP) induces inflammatory signaling characterized by MAP kinase-mediated activation of NFkB and AP-1 in vitro and in bronchial biopsies obtained from human subjects exposed to DEP. NFkB and AP-1 activation results in the upregulation of genes involved in promoting inflammation in airway epithelial cells, a principal target of inhaled DEP. IL-8 is a proinflammatory chemokine expressed by the airway epithelium in response to environmental pollutants. The mechanism by which DEP exposure induces IL-8 expression is not well understood. In the current study, we sought to determine whether DEP with varying organic content induces IL-8 expression in lung epithelial cells, as well as, to develop a method to rapidly evaluate the upstream mechanism(s) by which DEP induces IL-8 expression. Exposure to DEP with varying organic content differentially induced IL-8 expression and IL-8 promoter activity human airway epithelial cells. Mutational analysis of the IL-8 promoter was also performed using recombinant human cell lines expressing reporters linked to the mutated promoters. Treatment with a low organic-containing DEP stimulated IL-8 expression by a mechanism that is predominantly NFkB-dependent. In contrast, exposure to high organic-containing DEP induced IL-8 expression independently of NFkB through a mechanism that requires AP-1 activity. Our study reveals that exposure to DEP of varying organic content induces proinflammatory gene expression through multiple specific mechanisms in human airway epithelial cells. The approaches used in the present study demonstrate the utility of a promoter-reporter assay ensemble for identifying transcriptional pathways activated by pollutant exposure.

  1. Sulforaphane inhibits de novo synthesis of IL-8 and MCP-1 in human epithelial cells generated by cigarette smoke extract.

    Science.gov (United States)

    Starrett, Warren; Blake, David J

    2011-06-01

    Chronic obstructive pulmonary disease (COPD) is currently the fifth leading cause of death worldwide. Exposure to cigarette smoke (CS) is the primary factor associated with the COPD development. CS activates epithelial cells to secrete chemokines such as interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) that recruit neutrophils and macrophages to the lung. These inflammatory cells then release additional chemokines and cytokines leading to chronic inflammation that initiates apoptosis in epithelial and endothelial cells and destruction of alveolar structure. Pulmonary epithelium responds to oxidative stress mediated by CS through activating NRF2-dependent pathways, leading to an increased expression of antioxidant and cytoprotective enzymes thereby providing a protective response against CS-induced lung injury. We hypothesized that activating NRF2-dependent cytoprotective gene expression with sulforaphane (SFN) affords protection against CS-induced lung damage by inhibiting chemokine production. Results indicate that in the human BEAS-2B epithelial cell line, 5 μM SFN activated NRF2-dependent gene expression by triggering the translocation of NRF2 to the nucleus and significantly increased the expression of NRF2-dependent genes such as NADPH quinone oxidoreductase-1, heme oxygenase-1, and glutamate cysteine ligase modulatory subunit. Cigarette smoke extract (CSE) exposure of BEAS-2B cells significantly increased production of both IL-8 and MCP-1. Production of both chemokines was significantly reduced with SFN given prior to CSE; SFN inhibited IL-8 and MCP-1 gene expression at the transcription level. Our results indicate that activating NRF2 pathways with SFN inhibits CSE-induced chemokine production in human epithelial cells. However, the mechanism by which the production of chemokines is inhibited through SFN still remains to be elucidated. SFN may enhance NRF2 transcriptional activity resulting in the inhibition of proinflammatory pathways such

  2. Signal pathways underlying homocysteine-induced production of MCP-1 and IL-8 in cultured human whole blood

    Institute of Scientific and Technical Information of China (English)

    Xiao-kun ZENG; You-fei GUAN; Daniel G REMICK; Xian WANG

    2005-01-01

    Aim: To elucidate the mechanisms underlying homocysteine (Hcy)-induced chemokine production. Methods: Human whole blood was pretreated with inhibitors of calmodulin (CaM), protein kinase C (PKC), protein tyrosine kinase(PTK), mitogen-activated protein kinase (MAPK), and NF-κB and activators of PPARγ for 60 min followed by incubation with Hcy 100 μmol/L for 32 h. The levels of mitogen chemokine protein (MCP)-1 and interleukin-8 (IL-8) were determined by enzyme-linked immunosorbant assay (ELISA). Results: Inhibitors of PKC (calphostin C, 50-500 nmol/L and RO-31-8220, 10-100 nmol/L), CaM(W7, 28-280 μmol/L), ERK1/2 MAPK (PD 98059, 2-20 μmol/L), p38 MAPK(SB 203580, 0.6-6 μmol/L), JNK MAPK (curcumin, 2-10 μmol/L), and NF-κB(PDTC, 10-100 nmol/L) markedly reduced Hcy 100 μmol/L-induced production of MCP-1 and IL-8 in human cultured whole blood, but the inhibitors of PTK(genistein, 2.6-26 μmol/L and tyrphostin, 0.5-5 μmol/L) had no obvious effect on MCP-1 and IL-8 production. PPARγ activators (ciglitazone 30 μmol/L and troglitazone 10 μmol/L) depressed the Hcy-induced MCP-1 production but not IL-8 production in the cultured whole blood. Conclusion: Hcy-induced MCP-1 and IL-8 production is mediated by activated signaling pathways such as PKC,CaM, MAPK, and NF-κB. Our results not only provide clues for the signal transduction pathways mediating Hcy-induced chemokine production, but also offer a plausible explanation for a pathogenic role of hyperhomocysteinemia in these diseases.

  3. Cigarette smoke regulates the expression of TLR4 and IL-8 production by human macrophages

    Directory of Open Access Journals (Sweden)

    Rahman Irfan

    2009-05-01

    Full Text Available Abstract Background Toll-like receptors (TLRs are present on monocytes and alveolar macrophages that form the first line of defense against inhaled particles. The importance of those cells in the pathophysiology of chronic obstructive pulmonary disease (COPD has well been documented. Cigarette smoke contains high concentration of oxidants which can stimulate immune cells to produce reactive oxygen species, cytokines and chemokines. Methods In this study, we evaluated the effects of cigarette smoke medium (CSM on TLR4 expression and interleukin (IL-8 production by human macrophages investigating the involvement of ROS. Results and Discussion TLR4 surface expression was downregulated on short term exposure (1 h of CSM. The downregulation could be explained by internalization of the TLR4 and the upregulation by an increase in TLR4 mRNA. IL-8 mRNA and protein were also increased by CSM. CSM stimulation increased intracellular ROS-production and decreased glutathione (GSH levels. The modulation of TLR4 mRNA and surface receptors expression, IRAK activation, IκB-α degradation, IL-8 mRNA and protein, GSH depletion and ROS production were all prevented by antioxidants such as N-acetyl-L-cysteine (NAC. Conclusion TLR4 may be involved in the pathogenesis of lung emphysema and oxidative stress and seems to be a crucial contributor in lung inflammation.

  4. Det chemokine system - en vigtig regulator af angiogenese i sundhed og sygdom

    DEFF Research Database (Denmark)

    Rosenkilde, Mette M; Schwartz, Thue W

    2004-01-01

    vigtig funktion chemokine systemet. Den chemokine-medieret regulering af angiogenese er meget sofistikeret og finjusteres, og omfatter pro-angiogene chemokines, for eksempel, CXCL8/IL8 interagere med CXCR2 receptoren, og anti-angiogene (dvs. angiostatic) chemokines, for eksempel, CXCL10/IP10...

  5. Enhanced chemosensitization in multidrug-resistant human breast cancer cells by inhibition of IL-6 and IL-8 production.

    Science.gov (United States)

    Shi, Zhi; Yang, Wei-Min; Chen, Li-Pai; Yang, Dong-Hua; Zhou, Qi; Zhu, Jin; Chen, Jun-Jiang; Huang, Ruo-Chun; Chen, Zhe-Sheng; Huang, Ruo-Pan

    2012-10-01

    Drug resistance remains a major hurdle to successful cancer treatment. Many mechanisms such as overexpression of multidrug-resistance related proteins, increased drug metabolism, decreased apoptosis, and impairment of signal transduction pathway can contribute multidrug resistance (MDR). Recent studies strongly suggest a close link between cytokines and drug resistance. To identify new targets involved in drug resistance, we established a multidrug-resistant human breast cancer cell line MCF-7/R and examined the cytokine profile using cytokine antibody array technology. Among 120 cytokines/chemokines screened, IL-6, IL-8, and 13 other proteins were found to be markedly increased in drug-resistant MCF-7/R cell line as compared to sensitive MCF-7/S cell line, while 7 proteins were specifically reduced in drug-resistant MCF-7/R cells. Neutralizing antibodies against IL-6 and IL-8 partially reversed the drug resistance of MCF-7/R to paclitaxel and doxorubicin, while a neutralizing antibody against MCP-1 had no significant effect. Inhibition of endogenous IL-6 or IL-8 by siRNA technology significantly enhanced drug sensitivity of MCF-7/R cells. Furthermore, overexpression of IL-6 or IL-8 expression by transfection increased the ADM resistance in MCF-7/S cells. Our data suggest that increased expression levels of IL-6 and IL-8 may contribute to MDR in human breast cancer cells.

  6. Regulatory Effect of E2, IL-6 and IL-8 on the Growth of Epithelial Ovarian Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Yue Wang; Jie Yang; Yan Gao; Yongrui Du; Leyuan Bao; Wenyan Niu; Zhi Yao

    2005-01-01

    To determine the regulatory effects of estrogen and cytokine IL-6 and IL-8 on the growth of epithelial ovarian cancer (OVCA), we first examined the status of estrogen receptors (ERα and ERβ), IL-6 receptor (IL-6Rα and gp130), and IL-8 receptor (IL-8RA and IL-8RB) on five epithelial OVCA cell lines by semiquantitative RT-PCR and Western blot analysis. Results showed that the expressions of these receptors were variable on the five cells.Those OVCA cells expressing the receptors were selected to study related molecular mechanism. MTT assay was performed to observe the effects of 17β-estradiol (E2), IL-6 and IL-8 on cell proliferation. We discovered that E2 markedly promoted the proliferation of CAOV-3 and OVCAR-3 cell in a time- and dose-dependent manner.Tamoxifen (Txf), an ER inhibitor, completely blocked the proliferation of the E2-induced cells, and IL-6- or/and IL-8-neutralizing antibody only showed partially blocking activity. IL-6 and IL-8 were able to significantly stimulate CAOV-3 and OVCAR-3 cell proliferation in a time- and dose-dependent manner, which had a potential synergistic effect on CAOV-3 cells but not on OVCAR-3 cells. The cell proliferation induced by these two cytokines was abolished completely by their specific neutralizing antibodies, partially by Txf, but not by unrelated goat IgG.Taken together, our results suggested that estrogen, IL-6 and IL-8 could modulate OVCA growth by forming a reciprocal cascade with amplifying effect. Cellular & Molecular Immunology.

  7. Wild-Type N-Ras, Overexpressed in Basal-like Breast Cancer, Promotes Tumor Formation by Inducing IL-8 Secretion via JAK2 Activation

    Directory of Open Access Journals (Sweden)

    Ze-Yi Zheng

    2015-07-01

    Full Text Available Basal-like breast cancers (BLBCs are aggressive, and their drivers are unclear. We have found that wild-type N-RAS is overexpressed in BLBCs but not in other breast cancer subtypes. Repressing N-RAS inhibits transformation and tumor growth, whereas overexpression enhances these processes even in preinvasive BLBC cells. We identified N-Ras-responsive genes, most of which encode chemokines; e.g., IL8. Expression levels of these chemokines and N-RAS in tumors correlate with outcome. N-Ras, but not K-Ras, induces IL-8 by binding and activating the cytoplasmic pool of JAK2; IL-8 then acts on both the cancer cells and stromal fibroblasts. Thus, BLBC progression is promoted by increasing activities of wild-type N-Ras, which mediates autocrine/paracrine signaling that can influence both cancer and stroma cells.

  8. Wild-Type N-Ras, Overexpressed in Basal-like Breast Cancer, Promotes Tumor Formation by Inducing IL-8 Secretion via JAK2 Activation.

    Science.gov (United States)

    Zheng, Ze-Yi; Tian, Lin; Bu, Wen; Fan, Cheng; Gao, Xia; Wang, Hai; Liao, Yi-Hua; Li, Yi; Lewis, Michael T; Edwards, Dean; Zwaka, Thomas P; Hilsenbeck, Susan G; Medina, Daniel; Perou, Charles M; Creighton, Chad J; Zhang, Xiang H-F; Chang, Eric C

    2015-07-21

    Basal-like breast cancers (BLBCs) are aggressive, and their drivers are unclear. We have found that wild-type N-RAS is overexpressed in BLBCs but not in other breast cancer subtypes. Repressing N-RAS inhibits transformation and tumor growth, whereas overexpression enhances these processes even in preinvasive BLBC cells. We identified N-Ras-responsive genes, most of which encode chemokines; e.g., IL8. Expression levels of these chemokines and N-RAS in tumors correlate with outcome. N-Ras, but not K-Ras, induces IL-8 by binding and activating the cytoplasmic pool of JAK2; IL-8 then acts on both the cancer cells and stromal fibroblasts. Thus, BLBC progression is promoted by increasing activities of wild-type N-Ras, which mediates autocrine/paracrine signaling that can influence both cancer and stroma cells.

  9. Pathogenic Escherichia coli and lipopolysaccharide enhance the expression of IL-8, CXCL5, and CXCL10 in canine endometrial stromal cells.

    Science.gov (United States)

    Karlsson, Iulia; Hagman, Ragnvi; Guo, Yongzhi; Humblot, Patrice; Wang, Liya; Wernersson, Sara

    2015-07-01

    Chemokines play a central role in cellular communication in response to bacterial infection. However, the knowledge of the chemokine responses to bacterial infections in dogs remains limited. Uterine bacterial infection (pyometra) is one of the most common bacterial diseases in dogs and causes sepsis in most of the cases. We have shown previously that dogs with pyometra have higher messenger RNA (mRNA) levels of chemokines in uterus. To assess whether the stromal part of the endometrium expresses chemokines in response to bacterial infection, we cultured endometrial stromal cells isolated from healthy dogs and exposed them to either live pathogenic Escherichia coli, isolated from the uterus of a dog with pyometra, or lipopolysaccharide. Changes in the mRNA expression of ELR(+) CXC chemokines, IL-8, CXCL5, CXCL7, and ELR(-) CXC chemokine, CXCL10, were measured after 24 hours using quantitative real-time polymerase chain reaction. Levels of IL-8, CXCL5, and CXCL10 were upregulated in endometrial stromal cells exposed to E coli and lipopolysaccharide, whereas the level of CXCL7 was decreased or unaffected. In addition, levels of IL-8 and CXCL5, but not CXCL7 or CXCL10, were significantly higher in dogs with pyometra than those in healthy dogs. Our findings show that pathogenic uterine-derived E coli induces a CXC chemokine response both in cultured endometrial stromal cells within 24 hours and in pyometra-affected uteri from dogs. Stromal cells could therefore play an important role in early neutrophil and T cell recruitment to the site of inflammation during gram-negative bacterial infection of the uterus. Further studies are needed to clarify the role of chemokines in host response to bacterial infection in dogs and the possibility of using chemokines as diagnostic parameters for bacterial infection in this species. PMID:25765298

  10. IL-8 and cathepsin B as melanoma serum biomarkers.

    Science.gov (United States)

    Zhang, Hongtao; Fu, Ting; McGettigan, Suzanne; Kumar, Suresh; Liu, Shujing; Speicher, David; Schuchter, Lynn; Xu, Xiaowei

    2011-01-01

    Melanoma accounts for only a small portion of skin cancer but it is associated with high mortality. Melanoma serum biomarkers that may aid early diagnosis or guide therapy are needed clinically. However, studies of serum biomarkers have often been hampered by the serum interference that causes false readouts in immunological tests. Here we show that, after using a special buffer to eliminate the serum interference, IL-8 and cathepsin B levels were significantly elevated in melanoma patients (p < 0.05). More importantly, the combination of IL-8 and cathepsin B were also studied as a prognosis marker for melanoma mortality. Our study provides a novel approach to examine serum biomarkers. PMID:21673904

  11. Berberine hydrochloride IL-8 dependently inhibits invasion and IL-8-independently promotes cell apoptosis in MDA-MB-231 cells.

    Science.gov (United States)

    Li, Xiang; Zhao, Shu-Juan; Shi, Hai-Lian; Qiu, Shui-Ping; Xie, Jian-Qun; Wu, Hui; Zhang, Bei-Bei; Wang, Zheng-Tao; Yuan, Jian-Ye; Wu, Xiao-Jun

    2014-12-01

    Breast cancer, the leading cause of cancer-related mortality worldwide in females, has high metastastic and recurrence rates. The aim of the present study was to evaluate the anti-metastatic and anticancer in situ effect of berberine hydrochloride (BER) in MDA-MB-231 cells. BER dose-dependently inhibited proliferation and the IL-8 secretion of MDA-MB-231 cells. Additional experiments revealed that the inactivation of PI3K, JAK2, NF-κB and AP-1 by BER contributed to the decreased IL-8 secretion. BER abrogated cell invasion induced by IL-8 accompanied with the downregulation of the gene expression of MMP-2, EGF, E-cadherin, bFGF and fibronectin. In addition, BER reduced cell motility but induced G2/M arrest and cell apoptosis in an IL-8‑independent manner. BER modulated multiple signaling pathway molecules involved in the regulation of cell apoptosis, including activation of p38 MAPK and JNK and deactivation of JAK2, p85 PI3K, Akt and NF-κB. The enhanced cell apoptosis induced by BER was eliminated by inhibitors of p38 MAPK and JNK but was strengthened by activator of p38 MAPK. Thus, BER inhibited cell metastasis partly through the IL-8 mediated pathway while it induced G2/M arrest and promoted cell apoptosis through the IL-8 independent pathway. Apoptosis induced by BER was mediated by crosstalks of various pathways including activation of p38 MAPK and JNK pathways and inactivation of Jak2/PI3K/NF-κB/AP-1 pathways. The results suggested that BER may be an efficient and safe drug candidate for treating highly metastatic breast cancer.

  12. A C-Terminal Coiled-Coil Region of CagL is Responsible for Helicobacter Pylori-Induced Il-8 Expression

    Science.gov (United States)

    Wiedemann, Tobias; Hofbaur, Stefan; Loell, Eva; Rieder, Gabriele

    2016-01-01

    Interleukin-8 (IL-8) is a potent neutrophil-activating chemokine which triggers the infiltration and migration of neutrophils into areas of bacterial infection. Helicobacter pylori-infected patient studies as well as animal models have revealed that H. pylori type I strains carrying an intact cytotoxin-associated gene pathogenicity island (cag-PAI) with a functional type IV secretion system (T4SS) induce IL-8 expression and secretion in gastric mucosa. This gastric mucosal IL-8 expression correlates with severe histological changes due to H. pylori infection. In the present study, we explored a new recognition pattern on the bacterial adhesion protein CagL inducing IL-8 expression in H. pylori-infected host cells. To analyze the secreted IL-8 concentration, we performed IL-8 enzyme-linked immunosorbent assay (ELISA). To investigate the H. pylori-induced IL-8 expression on the transcriptional level, we transiently transfected gastric epithelial cells (AGS) with a human IL-8 luciferase reporter construct. The results of this study demonstrate that specifically the C-terminal coiled-coil region of the H. pylori CagL protein, a protein described to be located on the tip of the T4SS-pilus, is responsible for several in vitro observations: 1) H. pylori-induced IL-8 secretion via the transforming growth factor (TGF)-α activated epidermal growth factor-receptor (EGF-R) signaling pathway; 2) H. pylori-induced elongation of the cells, a typical CagA-induced phenotype; and 3) the bridging of the T4SS to its human target cells. This novel bacterial-host recognition sequence allows a new insight into how H. pylori induces the inflammatory response in gastric epithelial cells and facilitates the development of precancerous conditions. PMID:27766167

  13. IL-8 Regulates The Epithelial-mesenchymal Transition (EMT) of Renal Cancer Through PKC/ERK Signaling Pathway%IL-8通过激活PKC/ERK信号通路促进肾癌细胞上皮细胞-间质细胞转化

    Institute of Scientific and Technical Information of China (English)

    毕良宽; 林天歆; 许可慰; 韩金利; 黄海; 张彩霞; 董文; 刘皓; 黄健

    2012-01-01

    上皮细胞-间质细胞转化(EMT)在肿瘤转移方面起着非常重要的作用.肾癌发生EMT的具体分子机制尚不清楚.IL-8是一个重要的炎症趋化因子,研究表明肾癌细胞可以分泌IL-8,但IL-8是否参与肾癌细胞EMT的调节目前尚无报道.我们研究发现,IL-8可以促进肾癌细胞形态发生间质化改变,IL-8刺激后E-钙黏蛋白表达水平下降,N-钙黏蛋白表达上调.另外,IL-8可以促进肾癌细胞侵袭,但对肾癌细胞增殖的影响并不明显.进一步研究显示,IL-8通过激活蛋白激酶C(PKC)引起细胞外调节性激酶(ERK)磷酸化.因此,我们认为IL-8可能通过PKC/ERK信号通路促进肾癌细胞发生EMT,这可能是肾癌转移的重要机制之一.%The epithelial-mesenchymal transition (EMT) is an essential component in tumor metastasis. However, the molecular mechanism of EMT in renal cancer is unclear. IL-8 is an important chemokine in tumor microenvironment. Studies have shown that renal cancer cells can secrete IL-8, whether it could induce EMT in renal cancer cells is unknown. Here we found that IL-8 could induce EMT in renal cancer cells. Upon the stimulation of IL-8, the expression of E-cadherin was up-regulated, while the expression of N-cadherin was down-regulated; IL-8 promoted the invasion of renal cancer cells, but there was no obvious impact on cell proliferation. In addition, IL-8 could activate ERK through PKC. Therefore, we believe that IL-8 may promote renal cancer EMT through PKC / ERK signaling pathway, which may be one of the important mechanisms of renal cancer metastasis.

  14. Tsr Chemoreceptor Interacts With IL-8 Provoking E. coli Transmigration Across Human Lung Epithelial Cells.

    Science.gov (United States)

    Han, Bing; Li, Manshu; Xu, Yonghao; Islam, Diana; Khang, Julie; Del Sorbo, Lorenzo; Lee, Warren; Szaszi, Katalin; Zhong, Nanshan; Slutsky, Arthur S; Li, Yimin; Zhang, Haibo

    2016-01-01

    Bacterial colonization of epithelial surfaces and subsequent transmigration across the mucosal barrier are essential for the development of infection. We hypothesized that the methyl-accepting proteins (MCPs), known as chemoreceptors expressed on Escherichia coli (E. coli) bacterial surface, play an important role in mediating bacterial transmigration. We demonstrated a direct interaction between human interleukin-8 (IL-8) and Tsr receptor, a major MCP chemoreceptor. Stimulation of human lung epithelial cell monolayer with IL-8 resulted in increased E. coli adhesion and transmigration of the native strain (RP437) and a strain expressing only Tsr (UU2373), as compared to a strain (UU2599) with Tsr truncation. The augmented E. coli adhesion and migration was associated with a higher expression of carcinoembryonic antigen-related cell adhesion molecule 6 and production of inflammatory cytokines/chemokines, and a lower expression of the tight junction protein claudin-1 and the plasma membrane protein caveolin-1 in lung epithelial cells. An increased E. coli colonization and pulmonary cytokine production induced by the RP437 and UU2373 strains was attenuated in mice challenged with the UU2599 strain. Our results suggest a critical role of the E. coli Tsr chemoreceptor in mediating bacterial colonization and transmigration across human lung epithelium during development of pulmonary infections.

  15. Extracellular acidification stimulates GPR68 mediated IL-8 production in human pancreatic β cells.

    Science.gov (United States)

    Chandra, Vikash; Karamitri, Angeliki; Richards, Paul; Cormier, Françoise; Ramond, Cyrille; Jockers, Ralf; Armanet, Mathieu; Albagli-Curiel, Olivier; Scharfmann, Raphael

    2016-01-01

    Acute or chronic metabolic complications such as diabetic ketoacidosis are often associated with extracellular acidification and pancreatic β-cell dysfunction. However, the mechanisms by which human β-cells sense and respond to acidic pH remain elusive. In this study, using the recently developed human β-cell line EndoC-βH2, we demonstrate that β-cells respond to extracellular acidification through GPR68, which is the predominant proton sensing receptor of human β-cells. Using gain- and loss-of-function studies, we provide evidence that the β-cell enriched transcription factor RFX6 is a major regulator of GPR68. Further, we show that acidic pH stimulates the production and secretion of the chemokine IL-8 by β-cells through NF-кB activation. Blocking of GPR68 or NF-кB activity severely attenuated acidification induced IL-8 production. Thus, we provide mechanistic insights into GPR68 mediated β-cell response to acidic microenvironment, which could be a new target to protect β-cell against acidosis induced inflammation. PMID:27166427

  16. Influence of interleukin-8 (IL-8) and IL-8 receptors on the migration of human keratinocytes, the role of PLC-γ and potential clinical implications

    OpenAIRE

    Jiang, Wen G; Sanders, Andrew J.; Ruge, Fiona; HARDING, KEITH G.

    2011-01-01

    Interleukin (IL)-8 is a pro-inflammatory cytokine that has a direct effect on immune cells, including polymorphonuclear cells. Keratinocytes are a rich source of IL-8. However, there is little knowledge on the role of IL-8 in clinical wound healing and the direct biological effect of IL-8 on keratinocytes. In this study, the effect of recombinant human IL-8 (rhIL-8) on migration and adhesion was tested using HaCaT keratinocytes as a cell model. The cell functions were evaluated using impedanc...

  17. Tumor necrosis factor (TNF)-alpha-induced IL-8 expression in gastric epithelial cells: role of reactive oxygen species and AP endonuclease-1/redox factor (Ref)-1.

    Science.gov (United States)

    O'Hara, Ann M; Bhattacharyya, Asima; Bai, Jie; Mifflin, Randy C; Ernst, Peter B; Mitra, Sankar; Crowe, Sheila E

    2009-06-01

    TNF-alpha contributes to oxidative stress via induction of reactive oxygen species (ROS) and pro-inflammatory cytokines. The molecular basis of this is not well understood but it is partly mediated through the inducible expression of IL-8. As redox factor-1 (Ref-1), is an important mediator of redox-regulated gene expression we investigated whether ROS and Ref-1 modulate TNF-alpha-induced IL-8 expression in human gastric epithelial cells. We found that TNF-alpha treatment of AGS cells enhanced nuclear expression of Ref-1 and potently induced IL-8 expression. Overexpression of Ref-1 enhanced IL-8 gene transcription at baseline and after TNF-alpha treatment whereas Ref-1 suppression and antioxidant treatment inhibited TNF-alpha-stimulated IL-8 expression. TNF-alpha-mediated enhancement of other pro-inflammatory chemokines like MIP-3 alpha and Gro-alpha was also regulated by Ref-1. Although TNF-alpha increased DNA binding activity of Ref-1-regulated transcription factors, AP-1 and NF-kappaB, to the IL-8 promoter, promoter activity was mainly mediated by NF-kappaB binding. Silencing of Ref-1 in AGS cells inhibited basal and TNF-alpha-induced AP-1 and NF-kappaB DNA binding activity, but not their nuclear accumulation. Collectively, we provide the first mechanistic evidence of Ref-1 involvement in TNF-alpha-mediated, redox-sensitive induction of IL-8 and other chemokines in human gastric mucosa. This has implications for understanding the pathogenesis of gastrointestinal inflammatory disorders.

  18. IL8 and Cathepsin B as Melanoma Serum Biomarkers

    Directory of Open Access Journals (Sweden)

    Xiaowei Xu

    2011-02-01

    Full Text Available Melanoma accounts for only a small portion of skin cancer but it is associated with high mortality. Melanoma serum biomarkers that may aid early diagnosis or guide therapy are needed clinically. However, studies of serum biomarkers have often been hampered by the serum interference that causes false readouts in immunological tests. Here we show that, after using a special buffer to eliminate the serum interference, IL-8 and cathepsin B levels were significantly elevated in melanoma patients (p < 0.05. More importantly, the combination of IL-8 and cathepsin B were also studied as a prognosis marker for melanoma mortality. Our study provides a novel approach to examine serum biomarkers.

  19. Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8.

    Science.gov (United States)

    Hartman, Zachary C; Poage, Graham M; den Hollander, Petra; Tsimelzon, Anna; Hill, Jamal; Panupinthu, Nattapon; Zhang, Yun; Mazumdar, Abhijit; Hilsenbeck, Susan G; Mills, Gordon B; Brown, Powel H

    2013-06-01

    Triple-negative breast cancers (TNBC) are aggressive with no effective targeted therapies. A combined database analysis identified 32 inflammation-related genes differentially expressed in TNBCs and 10 proved critical for anchorage-independent growth. In TNBC cells, an LPA-LPAR2-EZH2 NF-κB signaling cascade was essential for expression of interleukin (IL)-6, IL-8, and CXCL1. Concurrent inhibition of IL-6 and IL-8 expression dramatically inhibited colony formation and cell survival in vitro and stanched tumor engraftment and growth in vivo. A Cox multivariable analysis of patient specimens revealed that IL-6 and IL-8 expression predicted patient survival times. Together these findings offer a rationale for dual inhibition of IL-6/IL-8 signaling as a therapeutic strategy to improve outcomes for patients with TNBCs.

  20. Chemokine Signaling Specificity: Essential Role for the N-Terminal Domain of Chemokine Receptors†

    Science.gov (United States)

    N. Prado, Gregory; Suetomi, Katsutoshi; Shumate, David; Maxwell, Carrie; Ravindran, Aishwarya; Rajarathnam, Krishna; Navarro, Javier

    2009-01-01

    Chemokine IL-8 (CXCL8) binds to its cognate receptors CXCR1 and CXCR2 to induce inflammatory responses, wound healing, tumorogenesis, and neuronal survival. Here we identify the N-loop residues in IL-8 (H18 and F21) and the receptor N-termini as the major structural determinants regulating the rate of receptor internalization, which in turn controlled the activation profile of ERK1/2, a central component of the receptor/ERK signaling pathway that dictates signal specificity. Our data further support the idea that the chemokine receptor core acts as a plastic scaffold. Thus, the diversity and intensity of inflammatory and noninflammatory responses mediated by chemokine receptors appear to be primarily determined by the initial interaction between the receptor N-terminus and the N-loop of chemokines. PMID:17630697

  1. Variation in the CXCR1 gene (IL8RA is not associated with susceptibility to chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Scarel-Caminaga Raquel M

    2011-11-01

    Full Text Available Abstract Background The chemokine receptor 1 CXCR-1 (or IL8R-alpha is a specific receptor for the interleukin 8 (IL-8, which is chemoattractant for neutrophils and has an important role in the inflammatory response. The polymorphism rs2234671 at position Ex2+860G > C of the CXCR1 gene causes a conservative amino acid substitution (S276T. This single nucleotide polymorphism (SNP seemed to be functional as it was associated with decreased lung cancer risk. Previous studies of our group found association of haplotypes in the IL8 and in the CXCR2 genes with the multifactorial disease chronic periodontitis. In this study we investigated the polymorphism rs2234671 in 395 Brazilian subjects with and without chronic periodontitis. Findings Similar distribution of the allelic and genotypic frequencies were observed between the groups (p > 0.05. Conclusions The polymorphism rs2234671 in the CXCR1 gene was not associated with the susceptibility to chronic periodontitis in the studied Brazilian population.

  2. Molecular characterization and comparative expression analysis of two teleostean pro-inflammatory cytokines, IL-1β and IL-8, from Sebastes schlegeli.

    Science.gov (United States)

    Herath, H M L P B; Elvitigala, Don Anushka Sandaruwan; Godahewa, G I; Umasuthan, Navaneethaiyer; Whang, Ilson; Noh, Jae Koo; Lee, Jehee

    2016-01-10

    Interleukin 1β (IL-1β) and interleukin 8 (IL-8) are two major pro-inflammatory cytokines which play a central role in initiation of inflammatory responses against bacterial- and viral-infections. IL-1β is a member of the interleukin 1 family proteins and IL-8 is classified as a CXC-chemokine. In the current study, putative IL-1β and IL-8 counterparts were identified from a black rockfish transcriptomic database and designated as RfIL-1β and RfIL-8. The RfIL-1β cDNA sequence consists of 1140 nucleotides with a 759bp open reading frame (ORF) which encodes a 252 amino acid (aa) protein, whereas the RfIL-8 cDNA sequence (898bp) harbors a 300bp ORF encoding a 99 aa protein. Furthermore, the RfIL-1β aa sequence contains an IL-1 super family-like domain and an N-terminal IL-1 super family propeptide, while the amino acid sequence of RfIL-8 consists of a typical chemokine-CXC domain. Analysis of sequenced BAC clones containing RfIL-1β and RfIL-8 showed each gene to contain 4 exons interrupted by 3 introns. Pairwise comparison and phylogeny analysis of these cytokine sequences clearly revealed their closer relationship with other corresponding members of teleosts compared to birds and mammals. Constitutive differences in RfIL-1β and RfIL-8 mRNA expression were detected in a tissue-specific manner with the highest expression of each mRNA in spleen tissue. Two immune challenge experiments were conducted with Streptococcus iniae and polyinosinic:polycytidylic acid (poly I:C; a viral double stranded RNA mimic), and transcripts were quantified in spleen and peripheral blood cells. Significantly increased RfIL-1β and RfIL8 transcript levels were detected with almost similar profile patterns, further suggesting a putative involvement of these pro-inflammatory cytokines in the rockfish immunity. PMID:26449313

  3. Monocytes conditioned media stimulate fibronectin expression and spreading of inflammatory breast cancer cells in three-dimensional culture: A mechanism mediated by IL-8 signaling pathway

    Directory of Open Access Journals (Sweden)

    Mohamed Mona M

    2012-02-01

    Full Text Available Abstract Background Inflammatory breast cancer (IBC is the most aggressive form of breast cancer characterized by invasion of carcinoma cells into dermal lymphatic vessels where they form tumor emboli over expressing adhesion molecule E-cadherin. Although invasion and metastasis are dynamic processes controlled by complex interaction between tumor cells and microenvironment the mechanisms by which soluble mediators may regulate motility and invasion of IBC cells are poorly understood. The present study investigated the effect of media conditioned by human monocytes U937 secreted cytokines, chemokines and growth factors on the expression of adhesion molecules E-cadherin and fibronectin of human IBC cell line SUM149. Furthermore, cytokines signaling pathway involved were also identified. Results U937 secreted cytokines, chemokines and growth factors were characterized by cytokine antibody array. The major U937 secreted cytokines/chemokines were interleukin-8 (IL-8 and monocyte chemotactic protein-1 (MCP-1/CCL2. When SUM149 cells were seeded in three dimensional (3D models with media conditioned by U937 secreted cytokines, chemokines and growth factors; results showed: 1 changes in the morphology of IBC cells from epithelial to migratory spindle shape branched like structures; 2 Over-expression of adhesion molecule fibronectin and not E-cadherin. Further analysis revealed that over-expression of fibronectin may be mediated by IL-8 via PI3K/Akt signaling pathway. Conclusion The present results suggested that cytokines secreted by human monocytes may promote chemotactic migration and spreading of IBC cell lines. Results also indicated that IL-8 the major secreted cytokine by U937 cells may play essential role in fibronectin expression by SUM149 cells via interaction with IL-8 specific receptors and stimulation of PI3K/Akt signaling pathway.

  4. Effects of decoy molecules targeting NF-kappaB transcription factors in Cystic fibrosis IB3-1 cells: recruitment of NF-kappaB to the IL-8 gene promoter and transcription of the IL-8 gene.

    Science.gov (United States)

    Finotti, Alessia; Borgatti, Monica; Bezzerri, Valentino; Nicolis, Elena; Lampronti, Ilaria; Dechecchi, Maria; Mancini, Irene; Cabrini, Giulio; Saviano, Michele; Avitabile, Concetta; Romanelli, Alessandra; Gambari, Roberto

    2012-01-01

    One of the clinical features of cystic fibrosis (CF) is a deep inflammatory process, which is characterized by production and release of cytokines and chemokines, among which interleukin 8 (IL-8) represents one of the most important. Accordingly, there is a growing interest in developing therapies against CF to reduce the excessive inflammatory response in the airways of CF patients. Since transcription factor NF-kappaB plays a critical role in IL-8 expression, the transcription factor decoy (TFD) strategy might be of interest. In order to demonstrate that TFD against NF-kappaB interferes with the NF-kappaB pathway we proved, by chromatin immunoprecipitation (ChIP) that treatment with TFD oligodeoxyribonucleotides of cystic fibrosis IB3-1 cells infected with Pseudomonas aeruginosa leads to a decrease occupancy of the Il-8 gene promoter by NF-kappaB factors. In order to develop more stable therapeutic molecules, peptide nucleic acids (PNAs) based agents were considered. In this respect PNA-DNA-PNA (PDP) chimeras are molecules of great interest from several points of view: (1) they can be complexed with liposomes and microspheres; (2) they are resistant to DNases, serum and cytoplasmic extracts; (3) they are potent decoy molecules. By using electrophoretic mobility shift assay and RT-PCR analysis we have demonstrated that (1) the effects of PDP/PDP NF-kappaB decoy chimera on accumulation of pro-inflammatory mRNAs in P.aeruginosa infected IB3-1 cells reproduce that of decoy oligonucleotides; in particular (2) the PDP/PDP chimera is a strong inhibitor of IL-8 gene expression; (3) the effect of PDP/PDP chimeras, unlike those of ODN-based decoys, are observed even in the absence of protection with lipofectamine. These informations are of great impact, in our opinion, for the development of stable molecules to be used in non-viral gene therapy of cystic fibrosis. PMID:22772035

  5. MicroRNA-200c Represses IL-6, IL-8, and CCL-5 Expression and Enhances Osteogenic Differentiation

    Science.gov (United States)

    Sharp, Thad; Khorsand, Behnoush; Fischer, Carol; Eliason, Steven; Salem, Ali; Akkouch, Adil; Brogden, Kim; Amendt, Brad A.

    2016-01-01

    MicroRNAs (miRs) regulate inflammation and BMP antagonists, thus they have potential uses as therapeutic reagents. However, the molecular function of miR-200c in modulating proinflammatory and bone metabolic mediators and osteogenic differentiation is not known. After miR-200c was transduced into a human embryonic palatal mesenchyme (HEPM) (a cell line of preosteoblasts), using lentiviral vectors, the resulting miR-200c overexpression increased osteogenic differentiation biomarkers, including osteocalcin (OCN) transcripts and calcium content. miR-200c expression also down-regulated interleukin (IL)-6, IL-8, and chemokine (C-C motif) ligand (CCL)-5 under lipopolysaccharide (LPS) stimulation and increased osteoprotegerin (OPG) in these cells. miR-200c directly regulates the expression of IL-6, IL-8 and CCL-5 transcripts by binding to their 3’UTRs. A plasmid-based miR-200c inhibitor effectively reduces their binding activities. Additionally, miR-200c delivered using polyethylenimine (PEI) nanoparticles effectively inhibits IL-6, IL-8 and CCL-5 in primary human periodontal ligament fibroblasts and increases the biomarkers of osteogenic differentiation in human bone marrow mesenchymal stem cells (MSCs), including calcium content, ALP, and Runx2. These data demonstrate that miR-200c represses IL-6, IL-8 and CCL-5 and improves osteogenic differentiation. miR-200c may potentially be used as an effective means to prevent periodontitis-associated bone loss by arresting inflammation and osteoclastogenesis and enhancing bone regeneration. PMID:27529418

  6. Radiation results in IL-8 mediated intercellular signaling that increases adhesion between monocytic cells and aortic endothelium

    Science.gov (United States)

    Kucik, Dennis; Babitz, Stephen; Dunaway, Chad; Steele, Chad

    cells (HAECs) in vitro under conditions that mimic the shear stress in the bloodstream. For both heavy ions and x-rays, these adhesiveness changes are independent of adhesion molecule expression levels, but are chemokine dependent. Here we identify the specific endothelial chemokine responsible for this radiation-induced adhesiveness. X-irradiation increased IL-8 secretion almost 5-fold, while having little or no effect on expression of 15 other chemokines. Adhesiveness was then assayed under physiological shear stress using a flow chamber adhesion assay. Radiation significantly increased endothelial adhesiveness. The radiation-induced adhesiveness was specifically blocked by anti-IL-8 antibody, with no effect on baseline, radiation-independent adhesion. Addition of recombinant human IL-8 to un-irradiated HAECs was sufficient to increase adhesion to the same level as x-rays. Therefore, radiation-induced IL-8 signaling is both necessary and sufficient for radiation effects on aortic endothelial adhesiveness. This IL-8 induced adhesiveness may explain, at least in part, the mechanism by which radiation accelerates development of atherosclerosis. A better understanding of this mechanism can provide the basis for future countermeasure development.

  7. Electrochemical bioplatforms for the simultaneous determination of interleukin (IL)-8 mRNA and IL-8 protein oral cancer biomarkers in raw saliva.

    Science.gov (United States)

    Torrente-Rodríguez, R M; Campuzano, S; Ruiz-Valdepeñas Montiel, V; Gamella, M; Pingarrón, J M

    2016-03-15

    The development of electrochemical magnetobiosensors for the simultaneous determination of two biomarkers associated with salivary oral cancer, protein IL-8 and its messenger RNA (IL-8 mRNA) associated, in undiluted human saliva samples is reported in this work. The implemented methodology involves the use of functionalized magnetic beads, specific antibodies against IL-8 protein, a specific hairpin DNA sequence for IL-8 mRNA and amperometric detection at disposable dual screen printed carbon electrodes. This methodology exhibits high sensitivity and selectivity for the target analytes providing detection limits of 0.21 nM for IL-8 mRNA and 72.4 pgmL(-1) (far below the clinical established cut-off of 600 pgmL(-1)) for IL-8 protein in undiluted saliva samples. The dual amperometric magnetobiosensor was applied to the direct determination of both biomarkers in spiked raw saliva samples and to determine the endogenous content of IL-8 protein in saliva samples from 7 healthy individuals. The obtained results were statistically in agreement with those provided by a commercial ELISA kit.

  8. Human cytomegalovirus gene UL76 induces IL-8 expression through activation of the DNA damage response.

    Directory of Open Access Journals (Sweden)

    Helena Costa

    2013-09-01

    Full Text Available Human cytomegalovirus (HCMV, a β-herpesvirus, has evolved many strategies to subvert both innate and adaptive host immunity in order to ensure its survival and propagation within the host. Induction of IL-8 is particularly important during HCMV infection as neutrophils, primarily attracted by IL-8, play a key role in virus dissemination. Moreover, IL-8 has a positive effect in the replication of HCMV. This work has identified an HCMV gene (UL76, with the relevant property of inducing IL-8 expression at both transcriptional and protein levels. Up-regulation of IL-8 by UL76 results from activation of the NF-kB pathway as inhibition of both IKK-β activity or degradation of Ikβα abolishes the IL-8 induction and, concomitantly, expression of UL76 is associated with the translocation of p65 to the nucleus where it binds to the IL-8 promoter. Furthermore, the UL76-mediated induction of IL-8 requires ATM and is correlated with the phosphorylation of NEMO on serine 85, indicating that UL76 activates NF-kB pathway by the DNA Damage response, similar to the impact of genotoxic drugs. More importantly, a UL76 deletion mutant virus was significantly less efficient in stimulating IL-8 production than the wild type virus. In addition, there was a significant reduction of IL-8 secretion when ATM -/- cells were infected with wild type HCMV, thus, indicating that ATM is also involved in the induction of IL-8 by HCMV. In conclusion, we demonstrate that expression of UL76 gene induces IL-8 expression as a result of the DNA damage response and that both UL76 and ATM have a role in the mechanism of IL-8 induction during HCMV infection. Hence, this work characterizes a new role of the activation of DNA Damage response in the context of host-pathogen interactions.

  9. Genetic variants in the chemokines and chemokine receptors in Chagas disease.

    Science.gov (United States)

    Flórez, Oscar; Martín, Javier; González, Clara Isabel

    2012-08-01

    Clinical symptoms of Chagas' disease occur in 30% of the individuals infected with Trypanosoma cruzi and are characterised by heart inflammation and dysfunction. Chemokines and chemokine receptors control the migration of leukocytes during the inflammatory process and are involved in the modulation of Th1 or Th2 responses. To determine their influence, we investigated the possible role of CCL5/RANTES and CXCL8/IL8 chemokines, and CCR2 and CCR5 chemokines receptors cluster gene polymorphisms with the development of chagasic cardiomyopathy. Our study included 260 Chagas seropositive individuals (asymptomatic, n=130; cardiomyopathic, n=130) from an endemic area of Colombia. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and TaqMan SNP genotyping assay. We found statistically significant differences in the distribution of the CCR5 human haplogroup (HH)-A (p=0.027; OR=3.78, 95% CI=1.04-13.72). Moreover, we found that the CCR5-2733 G and CCR5-2554 T alleles are associated, respectively, with a reduced risk of susceptibility and severity to develop chagasic cardiomyopathy. No other associations were found to be significant for the other polymorphisms analysed in the CCR5, CCR2, CCL5/RANTES and CXCL8/IL8 genes. Our data suggest that the analysed chemokines and chemokine receptor genetic variants have a weak but important association with the development of chagasic cardiomyopathy in the population under study.

  10. MEK-dependent IL-8 induction regulates the invasiveness of triple-negative breast cancer cells.

    Science.gov (United States)

    Kim, Sangmin; Lee, Jeongmin; Jeon, Myeongjin; Lee, Jeong Eon; Nam, Seok Jin

    2016-04-01

    Interleukin-8 (IL-8) serves as a prognostic marker for breast cancer, and its expression level correlates with metastatic breast cancer and poor prognosis. Here, we investigated the levels of IL-8 expression in a variety of breast cancer cells and the regulatory mechanism of IL-8 in triple-negative breast cancer (TNBC) cells. Our results showed that IL-8 expression correlated positively with overall survival in basal-type breast cancer patients. The levels of IL-8 mRNA expression and protein secretion were significantly increased in TNBC cells compared with non-TNBC cells. In addition, the invasiveness of the TNBC cells was dramatically increased by IL-8 treatment and then augmented invasion-related proteins such as matrix metalloproteinase (MMP)-2 or MMP-9. We observed that elevated IL-8 mRNA expression and protein secretion were suppressed by a specific MEK1/2 inhibitor, UO126. In contrast, the overexpression of constitutively active MEK significantly increased the level of IL-8 mRNA expression in BT474 non-TNBC cells. Finally, we investigated the effect of UO126 on the tumorigenecity of TNBC cells. Our results showed that anchorage-independent growth, cell invasion, and cell migration were also decreased by UO126 in TNBC cells. As such, we demonstrated that IL-8 expression is regulated through MEK/ERK-dependent pathways in TNBC cells. A diversity of MEK blockers, including UO126, may be promising for treating TNBC patients.

  11. Correlation of IL-8 with induction, progression and metastatic potential of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the expression profile of IL-8 in inflammatory and malignant colorectal diseases to evaluate its potential role in the regulation of colorectal cancer (CRC) and the development of colorectal liver metastases (CRLM).METHODS: IL-8 expression was assessed by quantitative real-time PCR (Q-RT-PCR) and the enzyme-linked immunosorbent assay (ELISA) in resected specimens from patients with ulcerative colitis (UC, n = 6)colorectal adenomas (CRA, n = 8), different stages of colorectal cancer (n = 48) as well as synchronous and metachronous CRLM along with their corresponding primary colorectal tumors (n = 16).RESULTS: IL-8 mRNA and protein expression was significantly up-regulated in all pathological colorectal entities investigated compared with the corresponding neighboring tissues. However, in the CRC specimens IL-8 revealed a significantly more pronounced overexpression in relation to the CRA and UC tissues with an average 30-fold IL-8 protein up-regulation in the CRC specimens in comparison to the CRA tissues. Moreover, IL-8 expression revealed a close correlation with tumor grading. Most interestingly, IL-8 up-regulation was most enhanced in synchronous and metachronous CRLM, if compared with the corresponding primary CRC tissues.Herein, an up to 80-fold IL-8 overexpression in individual metachronous metastases compared to normal tumor neighbor tissues was found.CONCLUSION: Our results strongly suggest an association between IL-8 expression, induction and progression of colorectal carcinoma and the development of colorectal liver metastases.

  12. IL-8-induced L-selectin shedding regulates its binding kinetics to PSGL-1

    Institute of Scientific and Technical Information of China (English)

    JIA XiaoLing; CHEN Juan; LONG Mian

    2009-01-01

    L-selectin plays a crucial role in inflammation cascade by initiating the tethering and rolling of leukocytes on endothelium wall.While many L-selectin molecules are rapidly shed from the cell surface upon activation,the remaining membrane-anchored L-selectin may still play an important role in regulating leukocyte rolling and adhesion with different binding kinetics.Here we developed an in vitro model to activate Jurkat cells via interlukin-8 (IL-8) and quantified the two-dimensional (2D) binding kinetics,using a micropipette aspiration assay,of membrane-anchored L-selectin to P-selectin glycoprotein ligand 1 (PSGL-1) ligand coupled onto human red blood cells (RBCs).The data indicated that L-selectin shedding reduced the amount of membrane-anchored L-selecUn and lowered both its reverse and forward rates.These results suggested that the rolling dynamics of activated leukocytes was determined by two opposite impacts:reducing the surface presentation would enhance the rolling but lowering the kinetic rates would decrease the rolling.This finding provides a new insight into understanding how L-selectin shedding regulates leukocyte rolling and adhesion.

  13. Fluoride-induced IL-8 release in human epithelial lung cells: Relationship to EGF-receptor-, SRC- and MAP-kinase activation

    International Nuclear Information System (INIS)

    Exposure of human epithelial lung cells to fluorides is known to induce a marked increase in the release of interleukin (IL)-8, a chemokine involved in neutrophil recruitment. In the present study, the involvement of mitogen-activating protein kinases (MAPKs), the role of upstream activation of Src family kinases (SFKs), epidermal growth factor receptor (EGFR) activation and the interrelationships between these pathways in fluoride-induced IL-8 were examined in a human epithelial lung cell line (A549). Sodium fluoride strongly activated MAPK, in particular JNK1/2 and p38. The ERK1/2-inhibitor PD98059, the p38-inhibitor SB202190 and the JNK1/2-inhibitor SP600125 partially inhibited the fluoride-induced IL-8 response. Combinations of these inhibitors reduced the responses nearly to basal levels. Treatment with siRNA against JNK2 also reduced the IL-8 response to fluoride. Furthermore, fluoride activated SFKs, which was abolished by the SFK-inhibitor PP2. PP2 substantially inhibited the increased levels of IL-8, and partially reduced the fluoride-induced activation of ERK1/2, p38 and JNK1/2. Fluoride exposure also led to a phosphorylation of the EGFR, that was partially inhibited by PP2. AG1478, an EGFR-inhibitor, partially reduced the fluoride-induced IL-8 response and the phosphorylation of JNK1/2 and ERK1/2, but less the phosphorylation of p38. The effects of AG1478 were less than that of PP2. In conclusion, our findings suggest that the fluoride-induced IL-8 release involves the combined activation of ERK1/2, JNK1/2 and p38, and that the phosphorylation of these kinases, and in particular JNK1/2 and ERK1/2, partly, is mediated via a SFK-dependent EGFR-linked pathway. SFK-dependent, but EGFR-independent mechanisms seem important, and especially for phosphorylation of p38

  14. Predictive Value of IL-8 for Sepsis and Severe Infections after Burn Injury - A Clinical Study

    Science.gov (United States)

    Kraft, Robert; Herndon, David N; Finnerty, Celeste C; Cox, Robert A; Song, Juquan; Jeschke, Marc G

    2014-01-01

    The inflammatory response induced by burn injury contributes to increased incidence of infections, sepsis, organ failure, and mortality. Thus, monitoring post-burn inflammation is of paramount importance but so far there are no reliable biomarkers available to monitor and/or predict infectious complications after burn. As IL-8 is a major mediator for inflammatory responses, the aim of our study was to determine whether IL-8 expression can be used to predict post-burn sepsis, infections, and mortality other outcomes post-burn. Plasma cytokines, acute phase proteins, constitutive proteins, and hormones were analyzed during the first 60 days post injury from 468 pediatric burn patients. Demographics and clinical outcome variables (length of stay, infection, sepsis, multiorgan failure (MOF), and mortality were recorded. A cut-off level for IL-8 was determined using receiver operating characteristic (ROC) analysis. Statistical significance is set at (p<0.05). ROC analysis identified a cut-off level of 234 pg/ml for IL-8 for survival. Patients were grouped according to their average IL-8 levels relative to this cut off and stratified into high (H) (n=133) and low (L) (n=335) groups. In the L group, regression analysis revealed a significant predictive value of IL-8 to percent of total body surface area (TBSA) burned and incidence of MOF (p<0.001). In the H group IL-8 levels were able to predict sepsis (p<0.002). In the H group, elevated IL-8 was associated with increased inflammatory and acute phase responses compared to the L group (p<0.05). High levels of IL-8 correlated with increased MOF, sepsis, and mortality. These data suggest that serum levels of IL-8 may be a valid biomarker for monitoring sepsis, infections, and mortality in burn patients. PMID:25514427

  15. IL-1β up-regulates expression of IL-8 in endometrial stromal cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Zhang Guiyu; Ren Shuwen; Zhang Youzhong; Yang Xingsheng

    2005-01-01

    Objective:To investigate the effects of interleukin-1beta (IL-1β) on expression of IL-8 in endometrial stromal cells (ESC) and evaluate the relationship between IL1 β and IL-8 ,and the significance of IL-1β in the development of endometriosis. Methods:The endometrial stromal cells obtained from patient with and without endometriosis cultured within 3 ~5 passage were exposed to various concentrations of IL-1β. The amount of IL-8 protein was assessed by ELISA. The expression of IL-8 mRNA was determined by RT-PCR. Results: 1. IL-8 protein was detected in culture supernatant of which the cells were not treated with IL-1β. The amount of IL-8 protein secretion increased obviously after stimulation with IL-1β at 1.0ng/ml for 4h and the peak of secretion was at 12h. 2. Expression of IL-8 mRNA was positive in unstimulated endometrial stromal cells. However, after stromal cells were incubated with IL-1β, the intensity of expression of IL-8 mRNA was obviously increased and demonstrated a dose-and timedependent manner. Increase of IL-8 mRNA was observed following stimulation with IL-1β for 4h ,and the peak at 12h. Conclusions:IL-1β induces endometrial stromal cell of endometriosis to express IL-8 not only at transcription level but also at post-transcription level. This up-regulation is dose-and time-dependent. IL-1β may play an important role in the onset of endometriosis.

  16. L-Ascorbyl-2-phosphate attenuates NF-κB signaling in SZ95 sebocytes without affecting IL-6 and IL-8 secretion.

    Science.gov (United States)

    Ikeno, Hiroshi; Apel, Mara; Zouboulis, Christos; Luger, Thomas A; Böhm, Markus

    2015-09-01

    Acne is the most common inflammatory skin disease. Interleukin-1 (IL-1) is at the beginning of the cytokine signaling cascade and may be involved in the pathogenesis of this disorder. It activates redox-sensitive transcription factors, which induce IL-6 and IL-8 expression. Interestingly, L-ascorbyl-2-phosphate (APS) was shown to have beneficial effects in patients with acne vulgaris. The mechanism of action of this agent remains unknown. Here, we investigated if APS attenuates IL-1β- or TNF-α-mediated IL-6 and IL-8 expression in SZ95 sebocytes, whereas TNF-α was used as control. We also explored NF-κB activation which is known to orchestrate IL-1β- and TNF-α-mediated cytokine expression in many cell types. Both IL-1β and TNF-α increased IL-6 and IL-8 mRNA expression in SZ95 sebocytes. However, only IL-1β induced IL-6 and IL-8 secretion. IL-1β but not TNF-α activated NF-κB canonical signaling as demonstrated by Iκ-Bα phosphorylation and degradation as well as by nuclear accumulation of NF-κB/p65. Concomitant treatment of SZ95 sebocytes with APS attenuated the effect of IL-1β and TNF-α on IL-6 and IL-8 gene expression as well as on IL-1β-mediated NF-κB signaling. In contrast, APS failed to reduce IL-1β-mediated IL-6 and IL-8 secretion, presumably by maintained IL-1β-mediated p38 activation, which is known to control IL-8 secretion. Our findings shed light into the impact of IL-1β on the inflammatory cytokine response and its molecular mechanisms in human sebocytes. Our data further suggest that the beneficial effect of APS in acne patients involves attenuation of NF-κB signaling but not reduction of IL-6 or IL-8 secretion. PMID:25894228

  17. TNF-α and IL-8 of the Patients with Allergic Asthma

    Institute of Scientific and Technical Information of China (English)

    LIU Guanghui; ZHU Rongfei; LI Baozhu

    2005-01-01

    Summary: The levels of serum TNF-α and IL-8 in the patients with allergic asthma during acute attack period and remission period, and the effects of glucocorticoid (GC) on them were investigated. By using ELISA, the levels of TNF-α and IL-8 were detected in the healthy volunteers (group C, n=40), the patients with allergic asthma (n=40) during acute attack period (group A) and remission period (group B) and those taking GC for a week (n=28). The results were compared among them. It was found that the levels of TNF-α and IL-8 in group A were higher than in group B and group C. In the patients subject to GC therapy, the levels of TNF-α and IL-8 were decreased as compared with those in group A. In group B, the level of TNF-α was higher than in group C, but there was no significant difference in the level of IL-8 between group B and group C. It was concluded that the inflammatory cytokines, TNF-α and IL-8, played important roles in the bronchus allergic inflammation. GC could reduce the levels of serum TNF-α and IL-8 to exert the anti-inflammatory effects.

  18. Candida albicans and Streptococcus salivarius modulate IL-6, IL-8, and TNF-alpha expression and secretion by engineered human oral mucosa cells.

    Science.gov (United States)

    Mostefaoui, Yakout; Bart, Christian; Frenette, Michel; Rouabhia, Mahmoud

    2004-11-01

    We investigated the involvement of oral epithelial cells via two cytokines (IL-6 and TNF-alpha) and one chemokine (IL-8) in local defences against live yeast (Candida albicans) and bacteria (Streptococcus salivarius) using an engineered human oral mucosa model. We report that the yeast changed from the blastospore to the hyphal form and induced significant tissue disorganization at later contact periods (24 and 48 h) compared to the bacteria. However, this effect did not reduce the viability or total number of epithelial cells. Gene activation analyses revealed that IL-6, IL-8 and TNF-alpha mRNA levels rose in tissues in contact with live C. albicans or S. salivarius. Gene activation was followed by an upregulation of protein secretion. IL-6 levels were higher after contact with C. albicans than with S. salivarius. IL-8 levels after contact with S. salivarius were higher than with C. albicans. Our study suggests that S. salivarius is more efficient at inducing proinflammatory mediator release than C. albicans. These results provide additional evidence for the contribution of oral epithelial cells to the inflammatory response against fungi and bacteria. PMID:15469436

  19. MEK activity controls IL-8 expression in tamoxifen-resistant MCF-7 breast cancer cells.

    Science.gov (United States)

    Kim, Sangmin; Jeon, Myeongjin; Lee, Jeong Eon; Nam, Seok Jin

    2016-04-01

    Although tamoxifen reduces disease progression, tamoxifen resistance occurs during the course of estrogen receptor-positive [ER+] breast cancer treatment. In the present study, we investigated the possibility that interleukin-8 (IL-8) is a prognostic marker for tamoxifen resistance and aimed to clarify the regulation of IL-8 expression in tamoxifen-resistant cells. Clinically, IL-8 expression is positively correlated with survival in luminal A type breast cancer patients, but not in luminal B type breast cancer patients. In addition, the levels of IL-8 mRNA and protein expression were significantly increased in tamoxifen-resistant (TamR) cells compared to tamoxifen-sensitive (TamS) cells. To determine the regulatory mechanism of IL-8 expression in TamR cells, we analyzed the activities of signaling molecules. Our results showed that the phosphorylation levels of MEK and Akt were markedly increased in TamR cells, but there was no change in the phosphorylation level of p38 MAPK. On the contrary, we observed that elevated IL-8 mRNA expression was suppressed by a specific MEK1/2 inhibitor, UO126, but not by the specific PI-3K inhibitor LY294002, in TamR cells, whereas, we found that overexpression of constitutively active-MEK (CA-MEK) significantly increased the levels of IL-8 mRNA expression in TamS cells. Finally, we investigated the effect of the specific CXCR1/2 inhibitor SB225002 on anchorage-independent growth of TamR cells, and found that the growth was completely suppressed by SB225002. Taken together, our results demonstrate that IL-8 expression is regulated through a MEK/ERK-dependent pathway in TamR cells, suggesting that IL-8 and its receptors may be promising therapeutic targets for overcoming tamoxifen resistance.

  20. IL-8 induces T cell chemotaxis, suppresses IL-4, and up-regulates IL-8 production by CD4+ T cells

    DEFF Research Database (Denmark)

    Gesser, B; Lund, Marianne; Lohse, N;

    1996-01-01

    Interleukin-8 (IL-8), a neutrophil-activating cytokine, also activates certain T cell functions such as chemotaxis. We additionally find (n = 6) that recombinant (rIL-8; 1-100 ng/ml), when added to 24 h culture of human CD4+ T cells, suppressed the spontaneous production of IL-4 (50-85%). Steady...... state production of Il-4 was typically around 30 pg/ml, determined by use of a solid- phase immunoabsorbant assay. De novo synthesis of IL-4 from CD4+ T cells cultured for 3 days was also evaluated by use of detection of [35S]methionine incorporation, as visualized by autoradiography of 2-D gels......, and showed that IL-8 suppressed IL-4 production. This suppression of IL-4 production was confirmed in the cytosol fraction by use of Western blotting. The effect of IL-8 (100 ng/ml) was comparable to that of 10 ng/ml recombinant interferon-gamma, both strongly suppressing IL-4 production. The regulatory...

  1. Decoy oligodeoxyribonucleotides and peptide nucleic acids-DNA chimeras targeting nuclear factor kappa-B: inhibition of IL-8 gene expression in cystic fibrosis cells infected with Pseudomonas aeruginosa.

    Science.gov (United States)

    Gambari, Roberto; Borgatti, Monica; Bezzerri, Valentino; Nicolis, Elena; Lampronti, Ilaria; Dechecchi, Maria Cristina; Mancini, Irene; Tamanini, Anna; Cabrini, Giulio

    2010-12-15

    Cystic fibrosis (CF) is characterized by a deep inflammatory process, with production and release of cytokines and chemokines, among which interleukin 8 (IL-8) represents one of the most important. Accordingly, there is a growing interest in developing therapies against IL-8, with the aim of reducing the excessive inflammatory response in the airways of CF patients. Since transcription factor NF-kappaB plays a critical role in IL-8 expression, the transcription factor decoy (TFD) strategy might be of interest. TFD is based on biomolecules mimicking the target sites of transcription factors (TFs) and able to interfere with TF activity when delivered to target cells. Here, we review the inhibitory effects of decoy oligodeoxyribonucleotides (ODNs) on expression of IL-8 gene and secretion of IL-8 by cystic fibrosis cells infected by Pseudomonas aeruginosa. In addition, the effects of decoy molecules based on peptide nucleic acids (PNAs) are discussed. In this respect PNA-DNA-PNA (PDP) chimeras are interesting: (a) unlike PNAs, they can be complexed with liposomes and microspheres; (b) unlike oligodeoxyribonucleotides (ODNs), they are resistant to DNAses, serum and cytoplasmic extracts; (c) unlike PNA/PNA and PNA/DNA hybrids, they are potent decoy molecules. Interestingly, PDP/PDP NF-kappaB decoy chimeras inhibit accumulation of pro-inflammatory mRNAs (including IL-8 mRNA) in P. aeruginosa infected IB3-1, cells reproducing the effects of decoy oligonucleotides. The effects of PDP/PDP chimeras, unlike ODN-based decoys, are observed even in absence of protection with lipofectamine. Since IL-8 is pivotal in pro-inflammatory processes affecting cystic fibrosis, inhibition of its functions might have a clinical relevance. PMID:20615393

  2. Predictive Value of IL-8 for Sepsis and Severe Infections after Burn Injury - A Clinical Study

    OpenAIRE

    Kraft, Robert; Herndon, David N; Finnerty, Celeste C.; Cox, Robert A.; Song, Juquan; Jeschke, Marc G.

    2015-01-01

    The inflammatory response induced by burn injury contributes to increased incidence of infections, sepsis, organ failure, and mortality. Thus, monitoring post-burn inflammation is of paramount importance but so far there are no reliable biomarkers available to monitor and/or predict infectious complications after burn. As IL-8 is a major mediator for inflammatory responses, the aim of our study was to determine whether IL-8 expression can be used to predict post-burn sepsis, infections, and m...

  3. Parainfluenza Virus Type 1 Induces Epithelial IL-8 Production via p38-MAPK Signalling

    Science.gov (United States)

    Galván Morales, Miguel Ángel; Cabello Gutiérrez, Carlos; Mejía Nepomuceno, Fidencio; Valle Peralta, Leticia; Valencia Maqueda, Elba; Manjarrez Zavala, María Eugenia

    2014-01-01

    Human parainfluenza virus type 1 (HPIV-1) is the most common cause of croup in infants. The aim of this study was to describe molecular mechanisms associated with IL-8 production during HPIV-1 infection and the role of viral replication in MAPK synthesis and activation. An in vitro model of HPIV-1 infection in the HEp-2 and A549 cell lines was used; a kinetic-based ELISA for IL-8 detection was also used, phosphorylation of the mitogen-activated protein kinases (MAPKs) was identified by Western blot analysis, and specific inhibitors for each kinase were used to identify which MAPK was involved. Inactivated viruses were used to assess whether viral replication is required for IL-8 production. Results revealed a gradual increase in IL-8 production at different selected times, when phosphorylation of MAPK was detected. The secretion of IL-8 in the two cell lines infected with the HPIV-1 is related to the phosphorylation of the MAPK as well as viral replication. Inhibition of p38 suppressed the secretion of IL-8 in the HEp-2 cells. No kinase activation was observed when viruses were inactivated. PMID:25013817

  4. Parainfluenza Virus Type 1 Induces Epithelial IL-8 Production via p38-MAPK Signalling

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Galván Morales

    2014-01-01

    Full Text Available Human parainfluenza virus type 1 (HPIV-1 is the most common cause of croup in infants. The aim of this study was to describe molecular mechanisms associated with IL-8 production during HPIV-1 infection and the role of viral replication in MAPK synthesis and activation. An in vitro model of HPIV-1 infection in the HEp-2 and A549 cell lines was used; a kinetic-based ELISA for IL-8 detection was also used, phosphorylation of the mitogen-activated protein kinases (MAPKs was identified by Western blot analysis, and specific inhibitors for each kinase were used to identify which MAPK was involved. Inactivated viruses were used to assess whether viral replication is required for IL-8 production. Results revealed a gradual increase in IL-8 production at different selected times, when phosphorylation of MAPK was detected. The secretion of IL-8 in the two cell lines infected with the HPIV-1 is related to the phosphorylation of the MAPK as well as viral replication. Inhibition of p38 suppressed the secretion of IL-8 in the HEp-2 cells. No kinase activation was observed when viruses were inactivated.

  5. Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells.

    Science.gov (United States)

    Singh, Jagdeep K; Simões, Bruno M; Howell, Sacha J; Farnie, Gillian; Clarke, Robert B

    2013-01-01

    Breast cancer stem-like cells (CSCs) are an important therapeutic target as they are purported to be responsible for tumor initiation, maintenance, metastases, and disease recurrence. Interleukin-8 (IL-8) is upregulated in breast cancer compared with normal breast tissue and is associated with poor prognosis. IL-8 is reported to promote breast cancer progression by increasing cell invasion, angiogenesis, and metastases and is upregulated in HER2-positive cancers. Recently, we and others have established that IL-8 via its cognate receptors, CXCR1 and CXCR2, is also involved in regulating breast CSC activity. Our work demonstrates that in metastatic breast CSCs, CXCR1/2 signals via transactivation of HER2. Given the importance of HER2 in breast cancer and in regulating CSC activity, a pathway driving the activation of these receptors would have important biological and clinical consequences, especially in tumors that express high levels of IL-8 and other CXCR1/2-activating ligands. Here, we review the IL-8 signaling pathway and the role of HER2 in maintaining an IL-8 inflammatory loop and discuss the potential of combining CXCR1/2 inhibitors with other treatments such as HER2-targeted therapy as a novel approach to eliminate CSCs and improve patient survival.

  6. Neutrophilic airways inflammation in lung cancer: the role of exhaled LTB-4 and IL-8

    Directory of Open Access Journals (Sweden)

    Orlando Silvio

    2011-06-01

    Full Text Available Abstract Background Recent advances in lung cancer biology presuppose its inflammatory origin. In this regard, LTB-4 and IL-8 are recognized to play a crucial role in neutrophil recruitment into airways during lung cancer. Notwithstanding the intriguing hypothesis, the exact role of neutrophilic inflammation in tumour biology remains complex and not completely known. The aim of this study was to give our contribution in this field by investigating LTB-4 and IL-8 in the breath condensate of NSCLC patients and verifying their role in cancer development and progression. Method We enrolled 50 NSCLC patients and 35 controls. LTB-4 and IL-8 concentrations were measured in the breath condensate and the blood of all the subjects under study using EIA kits. Thirty NSCLC patients and ten controls underwent induced sputum collection and analysis. Results LTB-4 and IL-8 resulted higher in breath condensate and the blood of NSCLC patients compared to controls. Significantly higher concentrations were found as the cancer stages progressed. A positive correlation was observed between exhaled IL-8 and LTB-4 and the percentage of neutrophils in the induced sputum. Conclusion The high concentrations of exhaled LTB-4 and IL-8 showed the presence of a neutrophilic inflammation in the airways of NSCLC patients and gave a further support to the inflammatory signalling in lung cancer. These exhaled proteins could represent a suitable non-invasive marker in the diagnosis and monitoring of lung cancer.

  7. Profiling Heparin-Chemokine Interactions Using Synthetic Tools

    Science.gov (United States)

    de Paz, Jose L.; Moseman, E. Ashley; Noti, Christian; Polito, Laura; von Andrian, Ulrich H.; Seeberger, Peter H.

    2009-01-01

    Glycosaminoglycans (GAGs), such as heparin or heparan sulfate, are required for the in vivo function of chemokines. Chemokines play a crucial role in the recruitment of leukocyte subsets to sites of inflammation and lymphocytes trafficking. GAG-chemokine interactions mediate cell migration and determine which leukocyte subsets enter tissues. Identifying the exact GAC sequences that bind to particular chemokines is key to understand chemokine function at the molecular level and develop strategies to interfere with chemokine-mediated processes. Here, we characterize the heparin binding profiles of eight chemokines (CCL21, IL-8, CXCL12, CXCL13, CCL19, CCL25, CCL28, and CXCL16) by employing heparin microarrays containing a small library of synthetic heparin oligosaccharides. The chemokines differ significantly in their interactions with heparin oligosaccharides: While some chemokines, (e.g., CCL21) strongly bind to a hexasaccharide containing the GlcNSO3(6-OSO3)-IdoA(2-OSO3) repeating unit, CCL19 does not bind and CXCL12 binds only weakly. The carbohydrate microarray binding results were validated by surface plasmon resonance experiments. In vitro chemotaxis assays revealed that dendrimers coated with the fully sulfated heparin hexasaccharide inhibit lymphocyte migration toward CCL21. Migration toward CXCL12 or CCL19 was not affected. These in vitro homing assays indicate that multivalent synthetic heparin dendrimers inhibit the migration of lymphocytes toward certain chemokine gradients by blocking the formation of a chemokine concentration gradient on GAG endothelial chains. These findings are in agreement with preliminary in vivo measurements of circulating lymphocytes. The results presented here contribute to the understanding of GAG-chemokine interactions, a first step toward the design of novel drugs that modulate chemokine activity. PMID:18030990

  8. fMLP-Induced IL-8 Release Is Dependent on NADPH Oxidase in Human Neutrophils

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    María A. Hidalgo

    2015-01-01

    Full Text Available N-Formyl-methionyl-leucyl-phenylalanine (fMLP and platelet-activating factor (PAF induce similar intracellular signalling profiles; but only fMLP induces interleukin-8 (IL-8 release and nicotinamide adenine dinucleotide phosphate reduced (NADPH oxidase activity in neutrophils. Because the role of ROS on IL-8 release in neutrophils is until now controversial, we assessed if NADPH oxidase is involved in the IL-8 secretions and PI3K/Akt, MAPK, and NF-κB pathways activity induced by fMLP. Neutrophils were obtained from healthy volunteers. IL-8 was measured by ELISA, IL-8 mRNA by qPCR, and ROS production by luminol-amplified chemiluminescence, reduction of ferricytochrome c, and FACS. Intracellular pH changes were detected by spectrofluorescence. ERK1/2, p38 MAPK, and Akt phosphorylation were analysed by immunoblotting and NF-κB was analysed by immunocytochemistry. Hydroxy-3-methoxyaceto-phenone (HMAP, diphenyleneiodonium (DPI, and siRNA Nox2 reduced the ROS and IL-8 release in neutrophils treated with fMLP. HMAP, DPI, and amiloride (a Na+/H+ exchanger inhibitor inhibited the Akt phosphorylation and did not affect the p38 MAPK and ERK1/2 activity. DPI and HMAP reduced NF-κB translocation induced by fMLP. We showed that IL-8 release induced by fMLP is dependent on NADPH oxidase, and ROS could play a redundant role in cell signalling, ultimately activating the PI3K/Akt and NF-κB pathways in neutrophils.

  9. Prognostic significance of IL-6 and IL-8 ascites levels in ovarian cancer patients

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    Piché Alain

    2011-05-01

    Full Text Available Abstract Background The acellular fraction of epithelial ovarian cancer (EOC ascites promotes de novo resistance of tumor cells and thus supports the idea that tumor cells may survive in the surrounding protective microenvironment contributing to disease recurrence. Levels of the pro-inflammatory cytokines IL-6 and IL-8 are elevated in EOC ascites suggesting that they could play a role in tumor progression. Methods We measured IL-6 and IL-8 levels in the ascites of 39 patients with newly diagnosed EOC. Commercially available enzyme-linked immunosorbent assay (ELISA was used to determine IL-6 and IL-8 ascites levels. Ascites cytokine levels were correlated with clinicopathological parameters and progression-free survival. Results Mean ascites levels for IL-6 and IL-8 were 6419 pg/ml (SEM: 1409 pg/ml and 1408 pg/ml (SEM: 437 pg/ml respectively. The levels of IL-6 and IL-8 in ascites were significantly lower in patients that have received prior chemotherapy before the surgery (Mann-Whitney U test, P = 0.037 for IL-6 and P = 0.008 for IL-8. Univariate analysis revealed that high IL-6 ascites levels (P = 0.021, serum CA125 levels (P = 0.04 and stage IV (P = 0.009 were significantly correlated with shorter progression-free survival. Including these variables in a multivariate analysis revealed that elevated IL-6 levels (P = 0.033 was an independent predictor of shorter progression-free survival. Conclusion Elevated IL-6, but not IL-8, ascites level is an independent predictor of shorter progression-free survival.

  10. α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8.

    LENUS (Irish Health Repository)

    Bergin, David A

    2010-12-01

    Hereditary deficiency of the protein α-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung. However, the reason for the increased neutrophil burden has not been fully elucidated. In this study we have demonstrated using human neutrophils that serum AAT coordinates both CXCR1- and soluble immune complex (sIC) receptor-mediated chemotaxis by divergent pathways. We demonstrated that glycosylated AAT can bind to IL-8 (a ligand for CXCR1) and that AAT-IL-8 complex formation prevented IL-8 interaction with CXCR1. Second, AAT modulated neutrophil chemotaxis in response to sIC by controlling membrane expression of the glycosylphosphatidylinositol-anchored (GPI-anchored) Fc receptor FcγRIIIb. This process was mediated through inhibition of ADAM-17 enzymatic activity. Neutrophils isolated from clinically stable AAT-deficient patients were characterized by low membrane expression of FcγRIIIb and increased chemotaxis in response to IL-8 and sIC. Treatment of AAT-deficient individuals with AAT augmentation therapy resulted in increased AAT binding to IL-8, increased AAT binding to the neutrophil membrane, decreased FcγRIIIb release from the neutrophil membrane, and normalization of chemotaxis. These results provide new insight into the mechanism underlying the effect of AAT augmentation therapy in the pulmonary disease associated with AAT deficiency.

  11. Purine-Metabolizing Ectoenzymes Control IL-8 Production in Human Colon HT-29 Cells

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    Fariborz Bahrami

    2014-01-01

    Full Text Available Interleukin-8 (IL-8 plays key roles in both chronic inflammatory diseases and tumor modulation. We previously observed that IL-8 secretion and function can be modulated by nucleotide (P2 receptors. Here we investigated whether IL-8 release by intestinal epithelial HT-29 cells, a cancer cell line, is modulated by extracellular nucleotide metabolism. We first identified that HT-29 cells regulated adenosine and adenine nucleotide concentration at their surface by the expression of the ectoenzymes NTPDase2, ecto-5′-nucleotidase, and adenylate kinase. The expression of the ectoenzymes was evaluated by RT-PCR, qPCR, and immunoblotting, and their activity was analyzed by RP-HPLC of the products and by detection of Pi produced from the hydrolysis of ATP, ADP, and AMP. In response to poly (I:C, with or without ATP and/or ADP, HT-29 cells released IL-8 and this secretion was modulated by the presence of NTPDase2 and adenylate kinase. Taken together, these results demonstrate the presence of 3 ectoenzymes at the surface of HT-29 cells that control nucleotide levels and adenosine production (NTPDase2, ecto-5′-nucleotidase and adenylate kinase and that P2 receptor-mediated signaling controls IL-8 release in HT-29 cells which is modulated by the presence of NTPDase2 and adenylate kinase.

  12. Effect of lead on IL-8 production and cell proliferation in human oral keratinocytes

    Institute of Scientific and Technical Information of China (English)

    Thaweboon Srosiri; Poomsawat Sopee; Thaweboon Boonyanit

    2010-01-01

    Objective:To investigate the effect of lead on the production of IL-8 and cell proliferation in normal human oral keratinocytes (NHKs). Methods: NHKs were prepared as outgrowths from normal human buccal mucosa. The cells were treated with three concentrations of lead glutamate (4.5í10-5M, 4.5í10-6M and 4.5í10-7M). NHKs grown in glutamic acid were used as control. The amounts of IL-8 secreted in the culture supernatants were evaluated at 12 and 24 h using enzyme-linked immunospecific assay (ELISA). Cell proliferation was determined by the MTT colorimetric assay. Three cultures were used for each experiment, and three independent experiments were performed. Analysis of variance and Duncan’s multiple range tests were used for statistical analysis. Results:An elevation of IL-8 in culture supernatants of NHKs treated with lead at all concentrations at 12 and 24 h after exposure in a dose-dependent manner was revealed. A significant increase in cell numbers was observed only at 24 h exposed to 4.5í10-5M lead glutamate. Conclusions: The capacity of NHKs, to secrete IL-8, enhanced by lead glutamate, is demonstrated here. Induction of cell proliferation is revealed only after exposure to high lead concentration. The elevation of secreted IL-8 is a probable initial sign for the acute inflammatory response and may be involved in the pathogenesis of lead stomatitis.

  13. Association of IL-8 (-251 A/T Gene Polymorphism with Clinical Parameters and Chronic Periodontitis

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    Hengameh Khosropanah

    2013-01-01

    Full Text Available Objective: To investigate the correlation between IL-8 (-251 A/T gene polymorphism and susceptibility to chronic periodontitis as well as different clinical parameters and severity of the condition in patients referred to dental school, Shiraz University of Medical Sciences, Shiraz, Iran.Materials and Methods: In this randomized cross sectional study, 227 non-smoking patients with chronic periodontitis (test and 40 healthy individuals (control were enrolled in this experiment and the following clinical parameters were employed in the study: Periodontal Pocket Depth (PPD, Clinical Attachment Level (CAL and Bone Loss (BL. All participants underwent the PCR (Polymerase Chain Reaction test to detect 251 A/T Single Nucleotide Polymorphism of IL8 gene.Results: No significant correlation was perceived between different genotypes of IL-8 and the severity of the periodontal condition (P= 0.164, neither did we detect any substantial association between different IL-8 genotypes and the mean PPD (P=0.525, CAL (P=0.151, BL (P=0.255, PI (P=0.087, BOP (P=0.265 and the average number of teeth (P=0.931.Conclusion: The results implied that there was no explicit correlation between 251 (A/T IL-8 gene polymorphism and the severity of the chronic periodontal disease or to the susceptibility to it.

  14. Predictive Value of IL-8 for Sepsis and Severe Infections After Burn Injury: A Clinical Study.

    Science.gov (United States)

    Kraft, Robert; Herndon, David N; Finnerty, Celeste C; Cox, Robert A; Song, Juquan; Jeschke, Marc G

    2015-03-01

    The inflammatory response induced by burn injury contributes to increased incidence of infections, sepsis, organ failure, and mortality. Thus, monitoring postburn inflammation is of paramount importance but, so far, there are no reliable biomarkers available to monitor and/or predict infectious complications after burn. As interleukin 8 (IL-8) is a major mediator for inflammatory responses, the aim of our study was to determine whether IL-8 expression can be used to predict postburn sepsis, infections, and mortality. Plasma cytokines, acute-phase proteins, constitutive proteins, and hormones were analyzed during the first 60 days after injury from 468 pediatric burn patients. Demographics and clinical outcome variables (length of stay, infection, sepsis, multiorgan failure [MOF], and mortality) were recorded. A cutoff level for IL-8 was determined using receiver operating characteristic analysis. Statistical significance is set at P Patients were grouped according to their average IL-8 levels relative to this cutoff and stratified into high (H) (n = 133) and low (L) (n = 335) groups. In the L group, regression analysis revealed a significant predictive value of IL-8 to percent of total body surface area burned and incidence of MOF (P inflammatory and acute-phase responses compared with the L group (P burn patients.

  15. l-Ascorbyl-2-phosphate attenuates NF-κB signaling in SZ95 sebocytes without affecting IL-6 and IL-8 secretion

    OpenAIRE

    Ikeno, Hiroshi; Apel, Mara; Zouboulis, Christos; Luger, Thomas A; Böhm, Markus

    2015-01-01

    Acne is the most common inflammatory skin disease. Interleukin-1 (IL-1) is at the beginning of the cytokine signaling cascade and may be involved in the pathogenesis of this disorder. It activates redox-sensitive transcription factors, which induce IL-6 and IL-8 expression. Interestingly, l-ascorbyl-2-phosphate (APS) was shown to have beneficial effects in patients with acne vulgaris. The mechanism of action of this agent remains unknown. Here, we investigated if APS attenuates IL-1β- or TNF-...

  16. CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hongkai; Zhuo, Yunyun; Hu, Xu; Shen, Weiwei; Zhang, Ying; Chu, Tongwei, E-mail: chtw@sina.com

    2015-03-06

    Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients. - Highlights: • Bone loss frequently results from lung cancer metastasis. • Cluster of differentiation (CD)147 was depleted in A549 lung adenocarcinoma cells. • RAW 264.7 cell osteoclastogenesis was blocked by medium from CD147-deficient cells. • Interleukin (IL)-8 level was reduced in the conditioned medium. • Osteoclastogenesis induced by lung tumor cells requires CD147-mediated IL-8 release.

  17. IL-8 dictates glycosaminoglycan binding and stability of IL-18 in cystic fibrosis.

    LENUS (Irish Health Repository)

    Reeves, Emer P

    2010-02-01

    Dysregulation of airway inflammation contributes to lung disease in cystic fibrosis (CF). Inflammation is mediated by inflammatory cytokines, including IL-8, which illustrates an increase in biological half-life and proinflammatory activity when bound to glycosaminoglycans (GAGs). The aim of this project was to compare IL-8 and IL-18 for their relative stability, activity, and interaction with GAGs, including chondroitin sulfate, hyaluronic acid, and heparan sulfate, present in high quantities in the lungs of patients with CF. Bronchoalveolar lavage fluid was collected from patients with CF (n = 28), non-CF controls (n = 14), and patients with chronic obstructive pulmonary disease (n = 12). Increased levels of IL-8 and reduced concentrations of IL-18 were detected in bronchial samples obtained from CF individuals. The low level of IL-18 was not a defect in IL-18 production, as the pro- and mature forms of the molecule were expressed and produced by CF epithelial cells and monocytes. There was, however, a marked competition between IL-8 and IL-18 for binding to GAGs. A pronounced loss of IL-18 binding capacity occurred in the presence of IL-8, which displaced IL-18 from these anionic-matrices, rendering the cytokine susceptible to proteolytic degradation by neutrophil elastase. As a biological consequence of IL-18 degradation, reduced levels of IL-2 were secreted by Jurkat T lymphocytes. In conclusion, a novel mechanism has been identified highlighting the potential of IL-8 to determine the fate of other inflammatory molecules, such as IL-18, within the inflammatory milieu of the CF lung.

  18. CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis

    International Nuclear Information System (INIS)

    Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients. - Highlights: • Bone loss frequently results from lung cancer metastasis. • Cluster of differentiation (CD)147 was depleted in A549 lung adenocarcinoma cells. • RAW 264.7 cell osteoclastogenesis was blocked by medium from CD147-deficient cells. • Interleukin (IL)-8 level was reduced in the conditioned medium. • Osteoclastogenesis induced by lung tumor cells requires CD147-mediated IL-8 release

  19. Association of duffy blood group gene polymorphisms with IL8 gene in chronic periodontitis.

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    Emília Ângela Sippert

    Full Text Available The antigens of the Duffy blood group system (DARC act as a receptor for the interleukin IL-8. IL-8 plays an important role in the pathogenesis of chronic periodontitis due to its chemotactic properties on neutrophils. The aim of this study was to investigate a possible association of Duffy blood group gene polymorphisms with the -353T>A, -845T>C and -738T>A SNPs of the IL8 gene in chronic periodontitis. One hundred and twenty-four individuals with chronic periodontitis and 187 controls were enrolled. DNA was extracted using the salting-out method. The Duffy genotypes and IL8 gene promoter polymorphisms were investigated by PCR-RFLP. Statistical analyses were conducted using the Chi square test with Yates correction or Fisher's Exact Test, and the possibility of associations were evaluated by odds ratio with a 95% confidence interval. When analyzed separately, for the Duffy blood group system, differences in the genotype and allele frequencies were not observed between all the groups analyzed; and, in nonsmokers, the -845C allele (3.6% vs. 0.4%, -845TC genotype (7.3% vs. 0.7% and the CTA haplotype (3.6% vs. 0.4% were positively associated with chronic periodontitis. For the first time to our knowledge, the polymorphisms of erythroid DARC plus IL8 -353T>A SNPs were associated with chronic periodontitis in Brazilian individuals. In Afro-Brazilians patients, the FY*02N.01 with IL8 -353A SNP was associated with protection to chronic periodontitis.

  20. Chemokines and Chemokine Receptors in Multiple Sclerosis

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    Wenjing Cheng

    2014-01-01

    Full Text Available Multiple sclerosis is an autoimmune disease with classical traits of demyelination, axonal damage, and neurodegeneration. The migration of autoimmune T cells and macrophages from blood to central nervous system as well as the destruction of blood brain barrier are thought to be the major processes in the development of this disease. Chemokines, which are small peptide mediators, can attract pathogenic cells to the sites of inflammation. Each helper T cell subset expresses different chemokine receptors so as to exert their different functions in the pathogenesis of MS. Recently published results have shown that the levels of some chemokines and chemokine receptors are increased in blood and cerebrospinal fluid of MS patients. This review describes the advanced researches on the role of chemokines and chemokine receptors in the development of MS and discusses the potential therapy of this disease targeting the chemokine network.

  1. Re: Chemokines in Cancer

    OpenAIRE

    Fehmi Narter

    2016-01-01

    Chemokines are chemotactic cytokines that regulate the trafficking and positioning of cells by activating the seven-transmembrane spanning G protein-coupled chemokine receptors (GPCR) or non G protein-coupled seven-transmembrane spanning receptors called atypical chemokine receptors (ACKR). Chemokines are basic proteins that also bind to glycosaminoglycans which play important roles in their biology. Chemokines are divided into four subfamilies based on the position of the first two N-termina...

  2. Cigarette smoke attenuates the production of cytokines by human plasmacytoid dendritic cells and enhances the release of IL-8 in response to TLR-9 stimulation

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    Mortaz Esmaeil

    2009-06-01

    Full Text Available Abstract Myeloid and plasmacytoid dendritic cells (mDCs, pDC are crucial to the immune system, detecting microorganisms and linking the innate and adaptive immunity. pDC are present in small quantities in tissues that are in contact with the external environment; mainly the skin, the inner lining of the nose, lungs, stomach and intestines. They produce large amounts of IFN-α after stimulation and are pivotal for the induction of antiviral responses. Chronic obstructive pulmonary disease (COPD patients are known to be more susceptible to viral infections. We have demonstrated that exposure of mDC to cigarette smoke extract (CSE leads to the release of chemokines, however, not much is known about the role of pDC in COPD. In this study, we addressed several key questions with respect to the mechanism of action of CSE on human pDC in an in vitro model. Human pDCs were isolated from normal healthy volunteers and subjected to fresh CSE and the levels of IL-8, TNF-α, IP-10, IL-6, IL-1, IL-12 and IL-10 and IFN-α were studied by both ELISA and real time PCR methods. We observed that CSE augmented the production of IL-8 and suppressed the release of TNF-α, IL-6 and IFN-α. Moreover, CSE suppressed PI3K/Akt signalling in pDC. In conclusion, our data indicate that CSE has both the potential to diminish anti-viral immunity by downregulating the release of IFN-α and other pro-inflammatory cytokines while, at the same time, augmenting the pathogenesis of COPD via an IL-8 induced recruitment of neutrophils.

  3. IL8 gene as modifier of cystic fibrosis: unraveling the factors which influence clinical variability.

    Science.gov (United States)

    Furlan, Larissa Lazzarini; Marson, Fernando Augusto Lima; Ribeiro, José Dirceu; Bertuzzo, Carmen Sílvia; Salomão Junior, João Batista; Souza, Dorotéia Rossi Silva

    2016-08-01

    The severity of cystic fibrosis (CF) is associated with classes of mutations in the CFTR gene (cystic fibrosis transmembrane regulator), physical environment and modifier genes interaction. The IL8 gene (interleukin 8), according to its respective polymorphisms, influences inflammatory responses. This study analyzed IL8 gene polymorphisms (rs4073, rs2227306 and rs2227307), by means of PCR/RFLP, and their association with pulmonary function markers and clinical severity scores in 186 patients with CF, considering the CFTR genotype. There was an association between rs2227307 and precocity of the disease. The severity of lung disease was associated with the following markers: transcutaneous arterial hemoglobin oxygen saturation (SaO2) (regardless of CFTR genotype, for the polymorphisms rs4073, rs2227306 and rs2227307); mucoid Pseudomonas aeruginosa (regardless of CFTR genotype, for the polymorphisms rs2227306 and rs2227307). Pulmonary function markers (SaO2 and spirometric variables) and clinical severity scores were also associated with IL8 gene polymorphisms. This study identified the IL8 gene, represented by rs4073 and rs2227306 polymorphisms, and particularly the rs2227307 polymorphism, as potentiating factors for the degree of variability in the severity of CF, especially in pulmonary clinical manifestation correlated with increased morbidity and mortality. PMID:27209008

  4. Status of circulating immune complexes, IL8 titers and cryoglobulins in patients with dengue infection.

    Science.gov (United States)

    Patra, Goutam; Ghosh, Manab; Modak, Dolanchampa; Bandopadhyay, Bhaswati; Saha, Bibhuti; Mukhopadhyay, Sumi

    2015-11-01

    Dengue, a serious viral infection caused by the mosquito vector, Aedes aegyptii, affects about 390 million people annually from more than 125 countries across the globe. However, until now, there is no reliable clinical or laboratory indicator to accurately predict the development of dengue severity. Here, we explored critical pathophysiological determinants like IL8, circulating immune complex (CIC) and cryoglobulin in dengue-infected patients for identification of novel dengue severity biomarker(s). Totally, 100 clinically suspected dengue cases were tested by NS1 ELISA and MAC ELISA for dengue virus aetiology. For control, 49 healthy volunteers were included. Blood profiling (complete hemogram and liver function test) of patient population were done using automated cell counter and standard auto analyzer based biochemical analysis. Serum CIC was quantified by PEG precipitation. Serum cryoglobulins were estimated by Folin assay. Levels of serum IL-8 were assessed by standard sandwich ELISA kits. Patient CIC were further characterized by SDS Gel electrophoresis. Forty per cent of the cases tested positive, of which 11 patients had severe clinical manifestation. The mean ±SEM of cryoglobulin concentration for DHF, DF, and HC were 1.30 ± 0.31, 0.59 ± 0.08 and 0.143 ± 0.009 μg/μl, respectively. Thus, DHF and DF patients have shown 9- and 2.2-fold increase in cryoglobulin levels; and 18- and 5-fold increased CIC, respectively compared to HC patients. The mean ±SEM of CIC-PEG index for DHF, DF and HC were 491 ± 41.22, 146 ± 14.19 and 27.98 ± 2.56, respectively. Raised levels of IL8 titers were also found in all 11 DHF patients. Peak levels of CIC, cryoglobulin and IL8 titers were associated with thrombocytopenia. SDS PAGE analysis of CIC from DHF revealed the presence of at least six protein bands that were not observed in samples from DF and HC. Prediction efficacy of IL8, CIC and cryoglobulin for DHF was determined using the receiver operator characteristic

  5. Porphyromonas gingivalis increases the invasiveness of oral cancer cells by upregulating IL-8 and MMPs.

    Science.gov (United States)

    Ha, Na Hee; Park, Dae Gun; Woo, Bok Hee; Kim, Da Jeong; Choi, Jeom Il; Park, Bong Soo; Kim, Yong Deok; Lee, Ji Hye; Park, Hae Ryoun

    2016-10-01

    Recent studies indicate that chronic inflammation promotes the aggressiveness of cancers. However, the direct molecular mechanisms underlying a functional link between chronic periodontitis, the most common form of oral inflammatory diseases, and the malignancy of oral cancer remain unknown. To elucidate the role of chronic periodontitis in progression of oral cancer, we examined the effect of Porphyromonas gingivalis (P. gingivalis), a major pathogen that causes chronic periodontitis, on the invasiveness of oral squamous cell carcinoma (OSCC) cells, including SCC-25, OSC-20 and SAS cells. Exposures to P. gingivalis promoted the invasive ability of OSC-20 and SAS cells via the upregulation of matrix metalloproteinases (MMPs), specifically MMP-1 and MMP-2. However, P. gingivalis-infected SCC-25 cells did not exhibit changes in their invasive properties or the low expression levels of MMPs. In an effort to delineate the molecular players that control the invasiveness, we first assessed the level of interleukin-8 (IL-8), a well-known inflammatory cytokine, in P. gingivalis-infected OSCC cells. IL-8 secretion was substantially increased in the OSC-20 and SAS cells, but not in the SCC-25 cells, following P. gingivalis infection. When IL-8 was directly applied to SCC-25 cells, their invasive ability and MMP level were significantly increased. Furthermore, the downregulation of IL-8 in P. gingivalis-infected OSC-20 and SAS cells attenuated their invasive potentials and MMP levels. Taken together, our findings strongly suggest that P. gingivalis infection plays an important role in the promotion of the invasive potential of OSCC cells via the upregulation of IL-8 and MMPs. PMID:27468958

  6. Prognostic evaluation of the B cell/IL-8 metagene in different intrinsic breast cancer subtypes.

    Science.gov (United States)

    Hanker, Lars C; Rody, Achim; Holtrich, Uwe; Pusztai, Lajos; Ruckhaeberle, Eugen; Liedtke, Cornelia; Ahr, Andre; Heinrich, Tomas M; Sänger, Nicole; Becker, Sven; Karn, Thomas

    2013-01-01

    We recently reported that a ratio of high B cell and low IL-8 metagene expression identified 32 % of triple negative breast cancers (TNBC) with good prognosis and was the only significant predictor in multivariate analysis including routine clinicopathological variables. However, the clinical relevance of this signature in other breast cancer subtypes remains unclear. We compiled Affymetrix gene expression datasets from 4,467 primary breast cancer samples and excluded 329 triple negative samples which were used as discovery cohort in our previous study. Molecular classification of the remaining 4,138 samples was performed by two methods, including single genes (ER, PgR, HER2, and Ki67) and a centroid-based method using the intrinsic gene list. The prognostic value within the respective subtypes was assessed by analyzing the event-free survival of patients as a function of the B cell/IL-8 metagene ratio using previously published cutoff. ER-negative subtypes had the highest expression of the B cell and the IL-8 metagenes. The IL-8/B cell signature assigned a considerable fraction of samples (range 20.7-42.0 %) into the "good prognosis" group. However, a significant prognostic value was only observed in the subgroup of triple negative breast cancer (P = 0.035). The prognostic value of the B cell/IL-8 ratio is mainly confined to the basal-like and TNBC subtypes of breast cancer. This result underlines the importance of subtype-specific analyses and suggests a sequential multistep approach to developing and applying outcome predictors in the clinic.

  7. TRAIL-inducedexpressionofuPAandIL-8 stronglyenhancedbyoverexpressionof TRAF2andBcl-xLinpancreaticductal adenocarcinomacells

    Institute of Scientific and Technical Information of China (English)

    Dong-Hui Zhou; Li-Na Yang; Christian Röder

    2013-01-01

    BACKGROUND: The death ligand, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), induces apoptosis and non-apoptotic signaling in some tumor cells. The purpose of this study was to investigate the roles of the pro-apoptotic TRAIL receptors, TRAIL-R1 and TRAIL-R2, as well as Bcl-xL and TRAF2 in TRAIL-induced expression of the pro-inlfammatory cytokine IL-8 and the invasion-promoting protein urokinase (uPA) in pancreatic ductal adenocarcinoma (PDAC) cells. METHODS: Colo357wt, Colo357/TRAF2, Colo357/Bcl-xL, Panc89 and PancTuI cells were stimulated with TRAIL and uPA and IL-8 expression was detected using real-time PCR. Antagonistic, receptor-speciifc antibodies were used to investigate the effects of TRAIL-R1 or TRAIL-R2 inhibition. RESULTS: Dose-dependent increases in uPA and IL-8 expression were detected following TRAIL stimulation in PDAC cells. These effects were inhibited when TRAIL-R1 but not TRAIL-R2 was blocked. Overexpression of TRAF2 or Bcl-xL strongly increased TRAIL-mediated upregulation of uPA and IL-8. CONCLUSIONS: In PDAC cells, TRAIL strongly induced uPA and IL-8 via TRAIL-R1. This response was further enhanced in cells overexpressing TRAF2 and Bcl-xL. Therefore, inhibition of the non-apoptotic "side-effects" of TRAIL treatments by inactivation of TRAF2 and Bcl-xL might represent additional relevant strategies for the treatment of pancreatic cancer.

  8. Endothelial cells overexpressing IL-8 receptor reduce cardiac remodeling and dysfunction following myocardial infarction.

    Science.gov (United States)

    Zhao, Xiangmin; Zhang, Wei; Xing, Dongqi; Li, Peng; Fu, Jinyan; Gong, Kaizheng; Hage, Fadi G; Oparil, Suzanne; Chen, Yiu-Fai

    2013-08-15

    The endothelium is a dynamic component of the cardiovascular system that plays an important role in health and disease. This study tested the hypothesis that targeted delivery of endothelial cells (ECs) overexpressing neutrophil membrane IL-8 receptors IL8RA and IL8RB reduces acute myocardial infarction (MI)-induced left ventricular (LV) remodeling and dysfunction and increases neovascularization in the area at risk surrounding the infarcted tissue. MI was created by ligating the left anterior descending coronary artery in 12-wk-old male Sprague-Dawley rats. Four groups of rats were studied: group 1: sham-operated rats without MI or EC transfusion; group 2: MI rats with intravenous vehicle; group 3: MI rats with transfused ECs transduced with empty adenoviral vector (Null-EC); and group 4: MI rats with transfused ECs overexpressing IL8RA/RB (1.5 × 10⁶ cells post-MI). Two weeks after MI, LV function was assessed by echocardiography; infarct size was assessed by triphenyltetrazolium chloride (live tissue) and picrosirus red (collagen) staining, and capillary density and neutrophil infiltration in the area at risk were measured by CD31 and MPO immunohistochemical staining, respectively. When compared with the MI + vehicle and MI-Null-EC groups, transfusion of IL8RA/RB-ECs decreased neutrophil infiltration and pro-inflammatory cytokine expression and increased capillary density in the area at risk, decreased infarct size, and reduced MI-induced LV dysfunction. These findings provide proof of principle that targeted delivery of ECs is effective in repairing injured cardiac tissue. Targeted delivery of ECs to infarcted hearts provides a potential novel strategy for the treatment of acute MI in humans.

  9. COPD和哮喘患者血清与支气管灌洗液中IL-8,SLPI,sCD14和sICAM-1含量比较%Serum and bronchial lavage fluid concentrations of IL-8, SLPI, sCD14 and sICAM-1 in patients with COPD and asthma

    Institute of Scientific and Technical Information of China (English)

    杨万勇; 陈波; 阮福旺

    2016-01-01

    目的:通过检测支气管灌洗(BAL)液与血清中趋化因子(IL-8),分泌性白细胞蛋白酶抑制剂(SLPI),可溶性细胞间粘附分子-1(sICAM-1)和sCD14含量,探讨IL-8、SLPI,sCD14和sICAM-1作为具有相似病程的哮喘和COPD患者炎症和免疫应答反应生物标志物的潜力。方法:采用酶联免疫法(ELISA)测定哮喘(n=13)与COPD (n=25)患者血清和支气管灌洗液中IL-8,SLPI,sCD14和sICAM-1含量。结果:哮喘和COPD患者BAL中IL-8和SLPI含量远高于血清中IL-8和SLPI含量,而BAL中sICAM-1和sCD14含量远低于血清中sICAM-1和sCD14含量。在测定的所有生物标志物中,COPD患者中只有BAL IL-8的浓度高于哮喘患者BAL IL-8的浓度。两组中, BAL IL-8与SLPI相关。COPD患者中,BAL sICAM-1和sCD14相关,而哮喘患者中BAL sICAM-1与FEV1/FVC相关。此外,哮喘患者中血清中SLPI与sCD14相关,且血清中sICAM-1与FEV1/FVC负相关。结论:分析特定生物标志物时,选择正确的生物流体至关重要。在测定的4个生物标志物中,COPD患者中只有BAL IL-8浓度高于哮喘患者BAL IL-8浓度。%Objectvie To quantify bronchial lavage (BAL) fluid and serum levels of chemokine (IL-8), secretory leukocyte protease inhibitor (SLPI), soluble intracellular adhesion molecules-1 (sICAM-1) and sCD14, as surrogate markers of inflamma-tory and immune response in asthma and chronic obstructive pulmonary disease (COPD) patients with similar disease duration time. Methods Biomarkers in serum and BAL fluid from asthma (n=13) and COPD (n=25) patients were detected by ELISA . Results We found that in asthma and COPD groups the concentrations of IL-8 and SLPI are significantly higher in BAL fluid than in serum, while levels of sICAM-1 and sCD14 in BAL fluid are significantly lower than in serum. Of these 4 measured bi-omarkers, only the BAL IL-8 was higher in COPD patients when compared to asthma. In both groups, BAL IL

  10. Digitoxin mimics gene therapy with CFTR and suppresses hypersecretion of IL-8 from cystic fibrosis lung epithelial cells

    OpenAIRE

    Srivastava, Meera; Eidelman, Ofer; Jian ZHANG; Paweletz, Cloud; Caohuy, Hung; Yang, QingFeng; Jacobson, Kenneth A.; Heldman, Eliahu; Huang, Wei; Jozwik, Catherine; Pollard, Bette S.; Pollard, Harvey B.

    2004-01-01

    Cystic fibrosis (CF) is a fatal, autosomal, recessive genetic disease that is characterized by profound lung inflammation. The inflammatory process is believed to be caused by massive overproduction of the proinflammatory protein IL-8, and the high levels of IL-8 in the CF lung are therefore believed to be the central mechanism behind CF lung pathophysiology. We show here that digitoxin, at sub nM concentrations, can suppress hypersecretion of IL-8 from cultured CF lung epithelial cells. Cert...

  11. COPD患者不同时期血清IL-8变化及其临床意义%Variation of Serum IL-8 with Different Stages in COPD Patients and Its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    李俊兰

    2008-01-01

    目的 探讨白介素-8(IL-8)参与COPD的发病机制及其与COPD预后的关系.方法 选择COPD急性发作期患者30例,测定新入院时及治疗后血浆IL-8水平,并与正常对照组比较.结果 COPD急性发作期患者IL-8水平明显高于正常组(P<0.05),治疗后好转组和恶化组患者IL-8水平仍然高于健康对照组(P<0.05).结论 IL-8参与了COPD气道炎症的发生发展,贯穿整个COPD病程始终.

  12. IL-1b, IL-6 and IL-8 Levels in Gyneco-Obstetric Infections

    Directory of Open Access Journals (Sweden)

    Beatriz Basso

    2005-01-01

    Full Text Available Objective. During pregnancy cytokines and inflammatory mediators stimulate the expression of prostaglandin, the levels of which determine the onset of labor. The aim of this work was to study interleukin IL-1β, IL-6 and IL-8 levels in the vaginal discharge, serum and urine of pregnant women with genitourinary infection before and after specific treatment. One hundred and fifty-one patients were studied during the second or third trimester of their pregnancy.

  13. Targeting IL-8 signalling to inhibit breast cancer stem cell activity.

    Science.gov (United States)

    Singh, Jagdeep K; Simões, Bruno M; Clarke, Robert B; Bundred, Nigel J

    2013-11-01

    Although survival from breast cancer has improved significantly over the past 20 years, disease recurrence remains a significant clinical problem. The concept of stem-like cells in cancer has been gaining currency over the last decade or so, since evidence for stem cell activity in human leukaemia and solid tumours, including breast cancer, was first published. Evidence indicates that this sub-population of cells, known as cancer stem-like cells (CSCs), is responsible for driving tumour formation and disease progression. In breast cancer, there is good evidence that CSCs are intrinsically resistant to conventional chemo-, radio- and endocrine therapies. By evading the effects of these treatments, CSCs are held culpable for disease recurrence. Hence, in order to improve treatment there is a need to develop CSC-targeted therapies. Interleukin-8 (IL-8), an inflammatory cytokine, is upregulated in breast cancer and associated with poor prognostic factors. Accumulating evidence demonstrates that IL-8, through its receptors CXCR1/2, is an important regulator of breast CSC activity. Inhibiting CXCR1/2 signalling has proved efficacious in pre-clinical models of breast cancer providing a good rationale for targeting CXCR1/2 clinically. Here, we discuss the role of IL-8 in breast CSC regulation and development of novel therapies to target CXCR1/2 signalling in breast cancer.

  14. Re: Chemokines in Cancer

    Directory of Open Access Journals (Sweden)

    Fehmi Narter

    2016-09-01

    Full Text Available Chemokines are chemotactic cytokines that regulate the trafficking and positioning of cells by activating the seven-transmembrane spanning G protein-coupled chemokine receptors (GPCR or non G protein-coupled seven-transmembrane spanning receptors called atypical chemokine receptors (ACKR. Chemokines are basic proteins that also bind to glycosaminoglycans which play important roles in their biology. Chemokines are divided into four subfamilies based on the position of the first two N-terminal cysteine residues, including the CC, CXC, CX3C and XC subfamilies. Nearly 50 chemokines and 20 signaling chemokine receptors and 4 AKCRs have been identified. Dysregulated expression of chemokines and their corresponding receptors is implicated in many diseases, such as autoimmune and inflammatory diseases and cancer. Chemokines are essential coordinators of cellular migration and cell-cell interactions and, therefore, have great impact on tumor development. In the tumor microenvironment, tumor-associated host cells and cancer cells release an array of different chemokines, resulting in the recruitment and activation of different cell types that mediate the balance between antitumor and pro-tumor responses. In addition to their primary role as chemoattractants, chemokines are also involved in other tumor-related processes, including tumor cell growth, angiogenesis and metastasis. Therefore, further studies of the distinctions between the pro-tumor and antitumor activities of chemokines are warranted in order to develop more effective therapies against cancer.

  15. Short-Chain Fatty Acids Regulate Secretion of IL-8 from Human Intestinal Epithelial Cell Lines in vitro.

    Science.gov (United States)

    Asarat, M; Vasiljevic, T; Apostolopoulos, V; Donkor, O

    2015-01-01

    Short-chain fatty acids (SCFAs) including acetate, propionate and butyrate play an important role in the physiological functions of epithelial cells and colonocytes, such as immune response regulation. Human intestinal epithelial cells (IECs) contribute in intestinal immune response via different ways, such as production of different immune factors including Interleukin (IL) IL-8, which act as chemoattractant for neutrophils, and subsequently enhance inflammation. Therefore, we aimed to evaluate the effects of SCFAs on IECs viability and production of IL-8 in vitro. SCFAs were co-cultured with either normal intestinal epithelial (T4056) or adenocarcinoma derived (HT-29) cell lines for 24-96 h in the presence of E.coli lipopolysaccharides (LPS). Cell viability, proliferation, production of IL-8 and expression of IL-8 mRNA were determined in the cell cultures. The result showed that 20 mM of SCFAs was non-cytotoxic to T4056 and enhanced their growth, whereas the growth of HT-29 was inhibited. The SCFAs down regulated LPS-stimulated IL-8 secretion with different response patterns, but no obvious effects on the release of IL-8 from non LPS- stimulated cells. In conclusion, SCFAs showed regulatory effect on release of LPS-stimulated IL-8 as well as the expression of mRNA of IL-8; these might explain the anti-inflammatory and anti-carcinogenic mechanism of SCFAs. PMID:26436853

  16. IL-8 secretion in primary cultures of prostate cells is associated with prostate cancer aggressiveness

    Directory of Open Access Journals (Sweden)

    Neveu B

    2014-05-01

    Full Text Available Bertrand Neveu*, Xavier Moreel*, Marie-Pier Deschênes-Rompré, Alain Bergeron, Hélène LaRue, Cherifa Ayari, Yves Fradet, Vincent FradetDepartment of Surgery, Laval University Cancer Research Centre, CHU de Quebec Research Centre, Quebec, QC, Canada *These authors contributed equally to this workBackground: Chronic inflammation is believed to be a major factor in prostate cancer initiation and promotion and has been studied using prostate cancer cells and immortalized cell lines. However, little is known about the contribution of normal cells to the prostatic microenvironment and inflammation. We aim to study the contribution of normal prostate epithelial cells to prostate inflammation and to link the inflammatory status of normal cells to prostate cancer aggressiveness.Materials and methods: Short-term primary cell cultures of normal epithelial prostate cells were derived from prostate biopsies from 25 men undergoing radical prostatectomy, cystoprostatectomy, or organ donation. Cells were treated with polyinosinic:polycytidylic acid, a mimic of double-stranded viral RNA and a potent inducer of the inflammatory response. Secretion of interleukin (IL-8 in the cell culture medium by untreated and treated cells was measured and we determined the association between IL-8 levels in these primary cell cultures and prostate cancer characteristics. The Fligner–Policello test was used to compare the groups.Results: Baseline and induced IL-8 secretion were highly variable between cultured cells from different patients. This variation was not related to drug use, past medical history, age, or preoperative prostate-specific antigen value. Nonetheless, an elevated secretion of IL-8 from normal cultured epithelial cells was associated with prostate cancer aggressiveness (P=0.0005.Conclusion: The baseline secretion of IL-8 from normal prostate epithelial cells in culture is strongly correlated with cancer aggressiveness and may drive prostate cancer

  17. The changes of sputum IL-8 and TNF-α level in COPD patients and their clinical value

    International Nuclear Information System (INIS)

    To investigate the changes and role of interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) in the diagnosis and therapy of COPD, the levels of IL-8 and TNF-α in serum and sputum samples in 58 COPD cases during different therapy periods were detected by radioimmunoassay. The results showed that the sputum IL-8 and TNF-α levels in COPD patients at the attack aggressive stage were significantly higher than those in the stable stage, which were in accord with those changes in serum samples. Furthermore, the changes of IL-8 and TNF-α levels in sputum samples were earlier than the changes in serum samples. The changes of sputum IL-8 and TNF-α levels in COPD patients may play a more important role than the changes of serum samples in the diagnosis and prognosis of patients with COPD. (authors)

  18. Luteolin 8-C-β-fucopyranoside inhibits invasion and suppresses TPA-induced MMP-9 and IL-8 via ERK/AP-1 and ERK/NF-κB signaling in MCF-7 breast cancer cells.

    Science.gov (United States)

    Park, Su-Ho; Kim, Jung-Hee; Lee, Dong-Hun; Kang, Jeong-Woo; Song, Hyuk-Hwan; Oh, Sei-Ryang; Yoon, Do-Young

    2013-11-01

    Matrix metalloproteinase 9 (MMP-9) and interleukin-8 (IL-8) play major roles in tumor progression and invasion of breast cancer cells. The present study was undertaken to investigate the inhibitory mechanism of cell invasion by luteolin 8-C-β-fucopyranoside (named as LU8C-FP), a C-glycosylflavone, in human breast cancer cells. We investigated whether LU8C-FP would inhibit MMP-9 activation and IL-8 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 breast cancer cells. LU8C-FP suppressed TPA-induced MMP-9 and IL-8 secretion and mRNA expression via inhibition of the MAPK signaling pathway and down-regulation of nuclear AP-1 and NF-κB. TPA-induced phosphorylation of ERK 1/2 was suppressed by LU8C-FP, whereas JNK and p38 MAPK phosphorylation were unaffected. In addition, LU8C-FP blocked the ERK 1/2 pathways following expression of MMP-9 and IL-8. These results suggest LU8C-FP may function to suppress invasion of breast cancer cells through the ERK/AP-1 and ERK/NF-κB signaling cascades.

  19. Association of IL8 and IL10 gene allelic variants with ischemic stroke risk and prognosis

    Directory of Open Access Journals (Sweden)

    Kucherenko A. M.

    2014-05-01

    Full Text Available Aim. Evaluating a role of IL8 gene –781 C/T, and IL10 gene –592C/A polymorphisms as genetic markers of ischemic stroke risk. Methods. A case group consisted of 183 patients with ischemic stroke, which were treated in the Brain Vascular Pathology unit of SI «Institute of Gerontology of NAMS of Ukraine». A control group included 88 healthy individuals older than 65 years without any history of ischemic stroke. Genotyping was performed using PCR followed by restriction fragment length polymorphism analysis. Results. Significantly (P < 0,05 higher frequency of IL8 –781T allele carriers in the case group (81,6 % comparing to the control (70,1% was revealed. –781T allele carriers have nearly 2-fold increased ischemic stroke development risk (OR = 1.886; 95 % CI: 1.041–3.417. Significantly (P < 0,05 higher frequency of IL10 gene –592C allele carriers was observed in the patients with ischemic stroke (98,2% comparing to the control (90,7 %. The ischemic stroke development risk in such individuals is 5-fold increased (OR = 5.71; 95 % CI: 1.48–22.11. It was revealed that –592C allele homozygotes with ischemic stroke have more than 2-fold higher improvement (according to the Rankin scale chances during the first fortnight of treatment (OR = 2,76; 95 % CI: 1,26–6,07. Conclusions. On the basis of the obtained significant differences, IL8 gene –781T and IL10 gene –592C variants may be considered the factors of ischemic stroke hereditary susceptibility. Besides, IL10 gene –592CC genotype is a genetic marker of the patients state positive dynamics during first two weeks of treatment.

  20. Expression ofVEGF,IL-6,IL-8 in serum and peritoneal fluid of patients with endometriosis

    Institute of Scientific and Technical Information of China (English)

    Yu-Xiang Fan

    2015-01-01

    Objective:To explore the expression of VEGF, IL-6, and IL-8 in serum and peritoneal fluid of patients with endometriosis (EMT) and their clinical significances.Methods:EMT patients who were pathologically diagnosed after laparoscopy from February, 2014 to February, 2015 were included in the study and served as the observation group. Moreover, patients with benign ovarian tumor and healthy women who came for physical examination at the same period were selected and served as the disease control group and normal control group, respectively for correlation analysis. The levels of VEGF, IL-6, and IL-8 in serum and peritoneal fluid of subjects in the three groups were compared.Results:The levels of serum VEGF, IL-6, and IL-8 in the observation group were significantly higher than those in the disease control group and the normal control group (P0.05). The levels of VEGF, IL-6, and IL-8 in peritoneal fluid in the observation group were significantly higher than those in the disease control group (P<0.05). With the increasing of EMT staging, the levels of VEGF, IL-6, and IL-8 in serum and peritoneal fluid were correspondingly elevated. The levels of VEGF, IL-6, and IL-8 in serum and peritoneal fluid at stageⅢ-Ⅳ were significantly higher than those at stageⅠ-Ⅱ(P<0.05).Conclusions:VEGF, IL-6 and IL-8 are highly expressed in serum and peritoneal fluid of patients with EMT. With the progression of the disease, the expression of VEGF, IL-6 and IL-8 shows an increasing trend. Clinical detection of the changes of VEGF, IL-6, and IL-8 levels in serum and peritoneal fluid can monitor the progression of EMT condition.

  1. Inhibition of PKC-Induced COX-2 and IL-8 Expression in Human Breast Cancer Cells by Glucosamine.

    Science.gov (United States)

    Chou, Wan-Yu; Chuang, Kun-Han; Sun, David; Lee, Yu-Hsiu; Kao, Pu-Hong; Lin, Yen-Yu; Wang, Hsei-Wei; Wu, Yuh-Lin

    2015-09-01

    Breast cancer is a common cancer leading to many deaths among females. Cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) are two highly expressed inflammatory mediators to be induced by the protein kinase C (PKC) signaling via various inflammatory stimuli and both contribute significantly to cancer metastasis/progression. Glucosamine has been shown to act as an anti-inflammation molecule. The aim of this study was to clarify the role and acting mechanism of glucosamine during the PKC-regulation of COX-2/IL-8 expression and the associated impact on breast cancer. In MCF-7 breast cancer cells, glucosamine effectively suppresses the PKC induction of COX-2 and IL-8 promoter activity, mRNA and protein levels, as well as the production of prostaglandin E(2) (PGE(2)) and IL-8. Glucosamine is able to promote COX-2 protein degradation in a calpain-dependent manner and IL-8 protein degradation in calpain-dependent and proteasome-dependent manners. The MAPK and NF-κB pathways are involved in PKC-induced COX-2 expression, but only the NF-κB pathway is involved in PKC-induced IL-8 expression. Glucosamine attenuates PKC-mediated IκBα phosphorylation, nuclear NF-κB translocation, and NF-κB reporter activation. Both PGE(2) and IL-8 promote cell proliferation and IL-8 induces cell migration; thus, glucosamine appears to suppress PKC-induced cell proliferation and migration. Furthermore, glucosamine significantly inhibits the growth of breast cancer xenografts and this is accompanied by a reduction in COX-2 and IL-8 expression. In conclusion, glucosamine seems to attenuate the inflammatory response in vitro and in vivo and this occurs, at least in part by targeting to the NF-κB signaling pathway, resulting in an inhibition of breast cancer cell growth.

  2. IFN-gamma Impairs Release of IL-8 by IL-1beta-stimulated A549 Lung Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Pfeilschifter Josef

    2008-09-01

    Full Text Available Abstract Background Production of interferon (IFN-γ is key to efficient anti-tumor immunity. The present study was set out to investigate effects of IFNγ on the release of the potent pro-angiogenic mediator IL-8 by human A549 lung carcinoma cells. Methods A549 cells were cultured and stimulated with interleukin (IL-1β alone or in combination with IFNγ. IL-8 production by these cells was analyzed with enzyme linked immuno sorbent assay (ELISA. mRNA-expression was analyzed by real-time PCR and RNase protection assay (RPA, respectively. Expression of inhibitor-κ Bα, cellular IL-8, and cyclooxygenase-2 was analyzed by Western blot analysis. Results Here we demonstrate that IFNγ efficiently reduced IL-8 secretion under the influence of IL-1β. Surprisingly, real-time PCR analysis and RPA revealed that the inhibitory effect of IFNγ on IL-8 was not associated with significant changes in mRNA levels. These observations concurred with lack of a modulatory activity of IFNγ on IL-1β-induced NF-κB activation as assessed by cellular IκB levels. Moreover, analysis of intracellular IL-8 suggests that IFNγ modulated IL-8 secretion by action on the posttranslational level. In contrast to IL-8, IL-1β-induced cyclooxygenase-2 expression and release of IL-6 were not affected by IFNγ indicating that modulation of IL-1β action by this cytokine displays specificity. Conclusion Data presented herein agree with an angiostatic role of IFNγ as seen in rodent models of solid tumors and suggest that increasing T helper type 1 (Th1-like functions in lung cancer patients e.g. by local delivery of IFNγ may mediate therapeutic benefit via mechanisms that potentially include modulation of pro-angiogenic IL-8.

  3. Serpina1 is a potent inhibitor of IL-8-induced hematopoietic stem cell mobilization

    DEFF Research Database (Denmark)

    van Pel, M.; van Os, R.; Velders, G.A.;

    2006-01-01

    Here, we report that cytokine-induced (granulocyte colony-stimulating factor and IL-8) hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) mobilization is completely inhibited after low-dose (0.5 Gy) total-body irradiation (TBI). Because neutrophil granular proteases......-dose TBI, both Serpina1 mRNA and protein concentrations were increased in BM extracts, compared with extracts that were obtained from controls. The inhibitory activity in BM extracts of irradiated mice was reversed by addition of an Ab directed against Serpina1. To further study a possible in vivo role...

  4. Effect of Panax notoginseng saponins on the content of IL-8 in serum after cerebral ischemia-reperfusion in rat

    International Nuclear Information System (INIS)

    Objective: To investigate the effect of Panax notoginseng saponins (Pns) against cerebral ischemia-reperfusion injury. Methods: Focal cerebral ischemia-reperal ischemia-reperfusion model in rat was established by occlusion the middle cerebral artery for 2 h, after 3 h reperfusion. The serum concentration of IL-8 was detected with radioimmunoassay (RIA). Results: Png 50 mg·kg-1 ip, qd x 7d before MCAO decreased the serum content of IL-8 after ischemia-reperfusion. Conclusion: Pns has protective effect against cerebral ischemia-reperfusion injury by decreased the serum content of IL-8

  5. Exercise-induced up-regulation of MMP-1 and IL-8 genes in endurance horses

    Directory of Open Access Journals (Sweden)

    Silvestrelli Maurizio

    2009-06-01

    Full Text Available Abstract Background The stress response is a critical factor in the training of equine athletes; it is important for performance and for protection of the animal against physio-pathological disorders. In this study, the molecular mechanisms involved in the response to acute and strenuous exercise were investigated using peripheral blood mononuclear cells (PBMCs. Results Quantitative real-time PCR (qRT-PCR was used to detect modifications in transcription levels of the genes for matrix metalloproteinase-1 (MMP-1 and interleukin 8 (IL-8, which were derived from previous genome-wide expression analysis. Significant up-regulation of these two genes was found in 10 horses that had completed a race of 90–120 km in a time-course experimental design. Conclusion These results suggest that MMP-1 and IL-8 are both involved in the exercise-induced stress response, and this represents a starting point from which to understand the adaptive responses to this phenomenon.

  6. IL-8, a novel messenger to cross-link inflammation and tumor EMT via autocrine and paracrine pathways (Review).

    Science.gov (United States)

    Long, Xinxin; Ye, Yingnan; Zhang, Lijie; Liu, Pengpeng; Yu, Wenwen; Wei, Feng; Ren, Xiubao; Yu, Jinpu

    2016-01-01

    The epithelial-mesenchymal transition (EMT) is a process through which epithelial cells trans-differentiate and acquire an aggressive mesenchymal phenotype. In tumor cells, EMT is a vital step of tumor progression and metastasis. Amid the increasing interest in tumor EMT, only a few studies focused on the soluble mediators secreted by tumor cells passing through this phenotypic switch. In this review, we focus on the essential role of interleukin-8 (IL-8) signaling for the acquisition and maintenance of tumor EMT via direct and indirect mechanisms. Besides the autocrine loop between IL-8 and tumor cells that have gone through EMT, IL-8 could potentiate adjacent epithelial tumor cells into a mesenchymal phenotype via a paracrine mode. Moreover, understanding the role of IL-8 in EMT will provide insight into the pathogenesis of tumor progression and may facilitate the development of an effective strategy for the prevention and treatment of metastatic cancer.

  7. The changes of IL-8, IL-10, IL-12 and IgE in serum of patients with asthma

    International Nuclear Information System (INIS)

    To evaluate the relationship and the clinical significance between the serum IL-8, IL-10, IL-12 and IgE in patients with asthma, the serum IL-8, IL-10 are measured by radioimmunoassay method and the serum IL-12, IgE by ELISA in 55 patients with asthma. The level of serum IL-8, IgE at stage of episode are significantly higher than that at stage of remission (P<0.01); the level of serum IL-10, IL-12 at stage of episode are significantly lower than that at stage of remission (P<0.01). Linear regression shows that the decrease of IL-12 relate to the increase of IgE. The results suggests that the change of the level of serum IL-8, IL-10, IL-12 and IgE could be a maker for the aggravation of asthma

  8. Identification of NR4A2 as a transcriptional activator of IL-8 expression in human inflammatory arthritis.

    LENUS (Irish Health Repository)

    Aherne, Carol M

    2009-10-01

    Expression of the orphan nuclear receptor NR4A2 is controlled by pro-inflammatory mediators, suggesting that NR4A2 may contribute to pathological processes in the inflammatory lesion. This study identifies the chemoattractant protein, interleukin 8 (IL-8\\/CXCL8), as a molecular target of NR4A2 in human inflammatory arthritis and examines the mechanism through which NR4A2 modulates IL-8 expression. In TNF-alpha-activated human synoviocyte cells, enhanced expression of IL-8 mRNA and protein correspond to temporal changes in NR4A2 transcription and nuclear distribution. Ectopic expression of NR4A2 leads to robust changes in endogenous IL-8 mRNA levels and co-treatment with TNF-alpha results in significant (p<0.001) secretion of IL-8 protein. Transcriptional effects of NR4A2 on the human IL-8 promoter are enhanced in the presence of TNF-alpha, suggesting molecular crosstalk between TNF-alpha signalling and NR4A2. A dominant negative IkappaB kinase antagonizes the combined effects of NR4A2 and TNF-alpha on IL-8 promoter activity. Co-expression of NR4A2 and the p65 subunit of NF-kappaB enhances IL-8 transcription and functional studies indicate that transactivation occurs independently of NR4A2 binding to DNA or heterodimerization with additional nuclear receptors. The IL-8 minimal promoter region is sufficient to support NR4A2 and NF-kappaB\\/p65 co-operative activity and NR4A2 can interact with NF-kappaB\\/p65 on a 39bp sequence within this region. In patients treated with methotrexate for active inflammatory arthritis, a reduction in NR4A2 synovial tissue levels correlate significantly (n=10, r=0.73, p=0.002) with changes in IL-8 expression. Collectively, these data delineate an important role for NR4A2 in modulating IL-8 expression and reveal novel transcriptional responses to TNF-alpha in human inflammatory joint disease.

  9. Expression and significance of IL-8 and MVD in the tissue of breast carcinoma%乳腺癌组织中IL-8和MVD的表达与预后关系

    Institute of Scientific and Technical Information of China (English)

    刘运江; 李明; 王小玲; 王永军; 刘月平

    2005-01-01

    目的:检测乳腺癌组织中IL-8和微血管密度(microvessel density,MVD)表达,探讨其与临床病理学因子及生物学因子的关系.方法:采用免疫组化SP法检测乳腺癌组织中IL-8、ER、PR、VEGF和CD105的表达.结果:1)103例乳腺癌组织中,IL-8阳性表达率为79.6%(82/103),正常及良性组织IL-8阳性率为13.8%(4/29),两者相比差异有统计学意义,P=0.000.2)MVD计数值范围为0~17.67,中位数为5.33.3)IL-8与VEGF和MVD表达均呈现正相关性,rs值分别为0.332和0.425,P值均为0.000.4)IL-8与淋巴结转移及临床分期有关,P值分别为0.002和0.024.5)IL-8与ER、PR、肿瘤大小及病理类型无关,P值分别为0.449、0.467、0.921和0.145.6)IL-8表达和MVD与乳腺癌预后有关,P值分别为0.006和0.002.结论:IL-8表达和MVD与影响乳腺癌患者预后的生物学因素相关,IL8和MVD高表达,预后差,可作为判断乳腺癌预后指标.

  10. Effect of G-CSF on induction of ENA-78 and IL-8 in the patients with malignant lymphoma.

    Science.gov (United States)

    Zhao, Wan-Hong; Meng, Shan; Tamura, Hideto; Kond, Asaka; Ogata, Kiyoyuki; Dan, Kazuo

    2014-04-01

    Granulocyte colony stimulating factor (G-CSF) restores neutrophil count in patients with chemotherapy-induced neutropenia. G-CSF can also induce production of epithelial neutrophil activating protein-78 (ENA-78) and interleukin-8 (IL-8), chemotactic factors from neutrophils in vitro. This study was purposed to investigate whether this effect is also observed in vivo. 10 lymphoma patients were selected who received chemotherapy and G-CSF (nartograstim) administration. Blood was obtained before chemotherapy [Time Point 1 (TP1)], at neutropenic phase before G-CSF administration (TP2), and at neutrophil recovery phase after G-CSF (TP3). ENA-78 and IL-8 mRNA in neutrophils were quantified by real-time PCR. Phagocytosis and reactive oxygen species (ROS) generation were examined by flow cytometry. The results showed that ENA-78 and IL-8 mRNA expression at TP2 increased in 5 and 8 patients, respectively. The ENA-78 mRNA expression at TP3 was increased in 3 and decreased in 6 patients, and IL-8 mRNA expression at TP3 decreased in 7 patients. G-CSF did not affect phagocytosis and normalized ROS generation in all of the patient. It is concluded that increase of ENA-78 and IL-8 expression in neutrophils is common in chemotherapy-induced neutropenic patients. G-CSF administration does not significantly increase ENA-78 and IL-8 expression.

  11. Comparison of IL-6, IL-8 Concentrations in H. pylori- and non-H. pylori-associated Gastritis

    Directory of Open Access Journals (Sweden)

    Gontar Alamsyah Siregar

    2014-12-01

    Full Text Available BACKGROUND: Helicobacter pylori is a non-invasive microorganism causing intense gastric mucosal inflammatory and immune reaction. The gastric mucosal levels of the proinflammatory cytokines Interleukin 6 (IL-6 and IL-8 have been reported to be increased in H. pylori infection, but the serum levels in H. pylori infection is still controversial. The purpose of this study was to investigate the serum levels of IL-6 and IL-8 in H. pylori infection. METHODS: A cross sectional study was done on eighty consecutive gastritis patients admitted to endoscopy units at Adam Malik General Hospital and Permata Bunda Hospital, Medan, Indonesia from May-October 2014. Histopathology was performed for the diagnosis of gastritis. Rapid urease test for diagnosis of H. pylori infection. Serum samples were obtained to determine circulating IL-6 and IL-8. Univariate and bivariate analysis (independent t test were done. RESULTS: There were 41.25% patients infected with H. pylori. Circulatory IL-6 levels were significantly higher in H. pylori-infected patients compared to H. pylori negative, but there were no differences between serum levels of IL-8 in H. pylori positive and negative patients. CONCLUSIONS: The immune response to H. pylori promotes systemic inflammation, which was reflected in an increased level of serum IL-6. Serum levels of IL-8 were not significantly different between H. pylori positive and negative. KEYWORDS: Helicobacter pylori, gastritis, IL-6, IL-8, cytokine.

  12. Chemokines, lymphocytes, and HIV

    Directory of Open Access Journals (Sweden)

    Farber J.M.

    1998-01-01

    Full Text Available Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-g and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3a, and STRL22 has been re-named CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit

  13. IL-6,IL-8与羊水栓塞的关系

    Institute of Scientific and Technical Information of China (English)

    吴琦

    2014-01-01

    羊水栓塞(Amniotic fluid embolism,AFE)指的是由于羊水及羊水的有形成分在分娩过程中进入母体血液循环而导致产妇过敏性休克、急性肺栓塞、肾功能衰竭、血管内凝血甚至出现猝死一系列严重临床症状的综合症。本文从AFE的病理变化、病因、高危因素以及发病机制与IL-6,IL-8关系四个方面对AFE作简要综述,旨在提高羊水栓塞临床诊断与治疗水平,降低孕产妇死亡率。

  14. Protein kinase A enhances lipopolysaccharide-induced IL-6, IL-8, and PGE2 production by human gingival fibroblasts

    Directory of Open Access Journals (Sweden)

    Ara Toshiaki

    2012-03-01

    Full Text Available Abstract Objective Periodontal disease is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss in severe clinical cases. Interleukin (IL-6, IL-8, and the chemical mediator prostaglandin E2 (PGE2 are known to play important roles in inflammatory responses and tissue degradation. Recently, we reported that the protein kinase A (PKA inhibitor H-89 suppresses lipopolysaccharide (LPS-induced IL-8 production by human gingival fibroblasts (HGFs. In the present study, the relevance of the PKA activity and two PKA-activating drugs, aminophylline and adrenaline, to LPS-induced inflammatory cytokines (IL-6 and IL-8 and PGE2 by HGFs were examined. Methods HGFs were treated with LPS from Porphyromonas gingivalis and H-89, the cAMP analog dibutyryl cyclic AMP (dbcAMP, aminophylline, or adrenaline. After 24 h, IL-6, IL-8, and PGE2 levels were evaluated by ELISA. Results H-89 did not affect LPS-induced IL-6 production, but suppressed IL-8 and PGE2 production. In contrast, dbcAMP significantly increased LPS-induced IL-6, IL-8, and PGE2 production. Up to 10 μg/ml of aminophylline did not affect LPS-induced IL-6, IL-8, or PGE2 production, but they were significantly increased at 100 μg/ml. Similarly, 0.01 μg/ml of adrenaline did not affect LPS-induced IL-6, IL-8, or PGE2 production, but they were significantly increased at concentrations of 0.1 and 1 μg/ml. In the absence of LPS, H-89, dbcAMP, aminophylline, and adrenaline had no relevance to IL-6, IL-8, or PGE2 production. Conclusion These results suggest that the PKA pathway, and also PKA-activating drugs, enhance LPS-induced IL-6, IL-8, and PGE2 production by HGFs. However, aminophylline may not have an effect on the production of these molecules at concentrations used in clinical settings (8 to 20 μg/ml in serum. These results suggest that aminophylline does not affect inflammatory responses in periodontal disease.

  15. IL-3、IL-5及IL-8与鼻息肉的关系研究%Relationship study between IL-3,IL-5 and IL-8 and Nasal polypus

    Institute of Scientific and Technical Information of China (English)

    赵雯

    2010-01-01

    Objective To explore the role of IL-3,IL-5 and IL-8 in the genesis and development of nasal polypus(NP) by testing IL-3 ,IL-5 and IL-8 Value in Nasal polypus issue. Methods 50 cases of nasal polyps and 30 casesof normal middle turbinate mucosa were involved in this study. Concentrations of IL-3, IL-5 and IL-8 were determined by enzyme linked immunosorbent assay(ELISA). Results The levels of IL-3 ,IL-5 and IL-8 in Nasal polypus issue were significantly higher than that in control group( P < 0.05 ). Conclusion The levels of IL-3, IL-5 and IL-8 in Nasal polypus issue rised,They likely played a certain role in the genesis and development of NP.%目的 检测鼻息肉组织中白细胞介素-3(IL-3)、白细胞介素-5(IL-5)和白细胞介素-8(IL-8)的含量,探讨细胞因子在鼻息肉形成中的作用.方法 标本取自50例鼻息肉患者的息肉组织(研究组)和30例行鼻中隔手术患者的正常下鼻甲黏膜(对照组),用酶联免疫吸附测定(ELISA)法检测IL-3、IL-5和IL-8在鼻息肉标本和正常下鼻甲黏膜的含量.结果 鼻息肉组织IL-3、IL-5和IL,-8的水平明显高于对照组,两组间差异有统计学意义(P<0.05).结论 IL,-3、IL-5和IL-8在鼻息肉组织中明显升高,提示其可能与鼻息肉的发病机制有关.

  16. Clinical Significance of Determination of Serum IL-6, IL-8 and TNF Contents in Patients with Lung Cancer%肺癌患者血清IL-6,IL-8和TNF活性测定的临床意义

    Institute of Scientific and Technical Information of China (English)

    吴家明

    2004-01-01

    目的:探讨了肺癌患者血清中IL-6、IL-8和TNF含量的变化.方法:应用酶联免疫吸附法和放免法测定了40例肺癌患者血清中IL-6、IL-8和TNF含量,且与35名正常健康人作比较.结果:肺癌患者血清中IL-6、IL-8和TNF水平均非常显著地高于正常人(P<0.01),术后IL-6、IL-8和TNF水平下降.结论:测定肺癌患者血清中IL-6、IL-8和TNF含量对判断患者的免疫状态有一定的临床价值.

  17. Effect of orthodontic force on inflammatory periodontal tissue remodeling and expression of IL-6 and IL-8 in rats

    Institute of Scientific and Technical Information of China (English)

    Jian-Hao Yang; Zheng-Chen Li; Wei-Dong Kong; Wu Zhang; Ying-Ping Jia; Yue-Lan Zhang; Lin-Bo Liu; Xue-Ping Han

    2013-01-01

    ABSTRACT Objective:To investigate effect of orthodontic force on inflammatory periodontal tissue remodeling and expression ofIL-6 andIL-8 in rats.Methods:EightySD rats were randomly divided into4 groups, blank control group(groupA) with5 rats, treatment normal group(group B) with25 rats, inflammation control group(group(groupC) with25 rats, inflammation treatment group(groupD) with25 rats.Immunohistochemistry and histomorphometric analysis was performed to measure the expression ofIL-6,IL-8 and the first molar to the recent movement in the distance.Results:The expression ofIL-8 reached a maximum on day5 and declined thereafter in groupB; the expression ofIL-6 reached a maximum on day5 in groupB.The expression ofIL-6 andIL-8 was gradually weakened with time in groupC.The expression of IL-6 andIL-8 were high, and reached a maximum on day5 and declined thereafter in groupD. AD of positive cells in groupD were higher than groupB at each time point(P<0.05).The time which0.49N orthodontic force was loaded was longer, orthodontic tooth movement distance was greater.Movement distance in groupD were longer than groupB(P<0.05).Conclusions:Orthodontic force as well as inflammatory stimulus can evoke the expression ofIL-6 andIL-8. Under the combined effects of inflammation and orthodontic force, the expression ofIL-6,IL-8 will increase.

  18. Fungus induces the release of IL- 8 in human corneal epithelial cells, via Dectin-1-mediated protein kinase C pathways

    Institute of Scientific and Technical Information of China (English)

    Xu-Dong; Peng; Gui-Qiu; Zhao; Jing; Lin; Nan; Jiang; Qiang; Xu; Cheng-Cheng; Zhu; Jian-Qiu; Qu; Lin; Cong; Hui; Li

    2015-01-01

    AIM: To identify whether Aspergillus fumigatus(A.fumigatus) hyphae antigens induced the release of interleukin-8(IL-8) in anti-fungal innate immunity of cultured human corneal epithelial cells(HCECs) and determine the involvement of intracellular signalling pathways. METHODS: HCECs were treated with A. fumigatus hyphae antigens with different concentrations and time.The cytoplasmic calcium of HCECs were assessed by fluorescence imaging. Western blot was used to detect the expression of Ca2 +-dependent protein kinase C(PKC). The IL-8 levels were determined by specific human IL-8 enzyme-linked immunosorbent assay(ELISA) and reverse transcriptase polymerase chain reaction(RT-PCR). Using a series of pharmacological inhibitors, we examined the upstream signalling pathway responsible for IL-8 expression in response to A.fumigatus hyphae antigens. RESULTS: Cells exposed to A. fumigatus hyphae antigens showed higher level of IL-8 m RNA expression and protein production. We demonstrated here that stimulation of HCECs with A. fumigatus hyphae triggers an intracellular Ca2 +flux and results in the activation of Ca2 +-dependent PKC(α, βⅠ and βⅡ) which can be attenuated by pre-treatment of cells with laminarin,suggesting that Dectin-1 signals pathway induced cytoplasmic calcium and influence the activation of PKC in HCECs. Inhibitors of Ca2 +-dependent PKC(Ro-31-8220 and Go6976) significantly abolished hyphae-induced expression of IL-8.CONCLUSION: Our findings suggest that A. fumigatushyphae-induced IL-8 expression was regulated by the activation of Dectin-1-mediated Ca2 +-dependent PKC in HCECs.

  19. Role of mechanical stretching and lipopolysaccharide in early apoptosis and IL-8 of alveolar epithelial typeⅡ cells A549

    Institute of Scientific and Technical Information of China (English)

    Qiao-Ming Ning; Xiao-Ning Sun; Xin-Kai Zhao

    2012-01-01

    Objective:To investigate the effects of mechanical stretching and lipopolysaccharide (LPS) on the early apoptosis and IL-8 production of alveolar epithelial typeⅡ cellsA549.Methods:The experimental matrix consisted of three integrated studies.In the first study,A549 cells were subjected to different stretching strain frequency and duration time to see the effects on the early apoptosis.In the second study,A549 cells were subjected to mechanical stretch(15%4 h, 0.5Hz) andLPS(1 or100 ng/mL) to see whether mechanical strain andLPS also have an addictive effect on the early apoptosis.In the third study to investigate whether this addictive effect could be induced byLPS and mechanical stretch onIL-8 production,A549 cells were subjected to LPS(100 ng/mL) and mechanical strain(15%,0.5Hz,4 h).Real timePCR and enzyme linked immunosorbent assay were used to measure mRNA and protein level ofIL-8.The early apoptosis was detected by flow cytometry.Results:Mechanical stretch induced the early apoptosis in a force and frequency and time-dependent manner.In the presence ofLPS, mechanical stretch enhancedLPS-induced early apoptosis, especially in100 ng/mLLPS group compared with1 ng/mLLPS and the control group.Mechanical stretch increasedIL-8 production and enhancedLPS-inducedIL-8 screation both in mRNA and protein levels.Conclusions:Mechanical stretch can induce the early apoptosis andIL-8 secretion.Mechanical stretch andLPS have an addictive effect on the early apoptosis andIL-8 production in alveolar type2 cells, which is one of the mechanisms of ventilator-induced lung injury.

  20. RNAi-based therapeutic nanostrategy: IL-8 gene silencing in pancreatic cancer cells using gold nanorods delivery vehicles

    Science.gov (United States)

    Panwar, Nishtha; Yang, Chengbin; Yin, Feng; Yoon, Ho Sup; Swee Chuan, Tjin; Yong, Ken-Tye

    2015-09-01

    RNA interference (RNAi)-based gene silencing possesses great ability for therapeutic intervention in pancreatic cancer. Among various oncogene mutations, Interleukin-8 (IL-8) gene mutations are found to be overexpressed in many pancreatic cell lines. In this work, we demonstrate IL-8 gene silencing by employing an RNAi-based gene therapy approach and this is achieved by using gold nanorods (AuNRs) for efficient delivery of IL-8 small interfering RNA (siRNA) to the pancreatic cell lines of MiaPaCa-2 and Panc-1. Upon comparing to Panc-1 cells, we found that the dominant expression of the IL-8 gene in MiaPaCa-2 cells resulted in an aggressive behavior towards the processes of cell invasion and metastasis. We have hence investigated the suitability of using AuNRs as novel non-viral nanocarriers for the efficient uptake and delivery of IL-8 siRNA in realizing gene knockdown of both MiaPaCa-2 and Panc-1 cells. Flow cytometry and fluorescence imaging techniques have been applied to confirm transfection and release of IL-8 siRNA. The ratio of AuNRs and siRNA has been optimized and transfection efficiencies as high as 88.40 ± 2.14% have been achieved. Upon successful delivery of IL-8 siRNA into cancer cells, the effects of IL-8 gene knockdown are quantified in terms of gene expression, cell invasion, cell migration and cell apoptosis assays. Statistical comparative studies for both MiaPaCa-2 and Panc-1 cells are presented in this work. IL-8 gene silencing has been demonstrated with knockdown efficiencies of 81.02 ± 10.14% and 75.73 ± 6.41% in MiaPaCa-2 and Panc-1 cells, respectively. Our results are then compared with a commercial transfection reagent, Oligofectamine, serving as positive control. The gene knockdown results illustrate the potential role of AuNRs as non-viral gene delivery vehicles for RNAi-based targeted cancer therapy applications.

  1. RNAi-based therapeutic nanostrategy: IL-8 gene silencing in pancreatic cancer cells using gold nanorods delivery vehicles.

    Science.gov (United States)

    Panwar, Nishtha; Yang, Chengbin; Yin, Feng; Yoon, Ho Sup; Chuan, Tjin Swee; Yong, Ken-Tye

    2015-09-11

    RNA interference (RNAi)-based gene silencing possesses great ability for therapeutic intervention in pancreatic cancer. Among various oncogene mutations, Interleukin-8 (IL-8) gene mutations are found to be overexpressed in many pancreatic cell lines. In this work, we demonstrate IL-8 gene silencing by employing an RNAi-based gene therapy approach and this is achieved by using gold nanorods (AuNRs) for efficient delivery of IL-8 small interfering RNA (siRNA) to the pancreatic cell lines of MiaPaCa-2 and Panc-1. Upon comparing to Panc-1 cells, we found that the dominant expression of the IL-8 gene in MiaPaCa-2 cells resulted in an aggressive behavior towards the processes of cell invasion and metastasis. We have hence investigated the suitability of using AuNRs as novel non-viral nanocarriers for the efficient uptake and delivery of IL-8 siRNA in realizing gene knockdown of both MiaPaCa-2 and Panc-1 cells. Flow cytometry and fluorescence imaging techniques have been applied to confirm transfection and release of IL-8 siRNA. The ratio of AuNRs and siRNA has been optimized and transfection efficiencies as high as 88.40 ± 2.14% have been achieved. Upon successful delivery of IL-8 siRNA into cancer cells, the effects of IL-8 gene knockdown are quantified in terms of gene expression, cell invasion, cell migration and cell apoptosis assays. Statistical comparative studies for both MiaPaCa-2 and Panc-1 cells are presented in this work. IL-8 gene silencing has been demonstrated with knockdown efficiencies of 81.02 ± 10.14% and 75.73 ± 6.41% in MiaPaCa-2 and Panc-1 cells, respectively. Our results are then compared with a commercial transfection reagent, Oligofectamine, serving as positive control. The gene knockdown results illustrate the potential role of AuNRs as non-viral gene delivery vehicles for RNAi-based targeted cancer therapy applications.

  2. Inflammatory cytokines IL-1 beta, IL-8, the relationship between the TNF alpha and breast cancer%炎症因子IL-1β、IL-8、TNF-α与乳腺癌的关系

    Institute of Scientific and Technical Information of China (English)

    景彩萍; 何静子; 魏晓丽

    2014-01-01

    研究发现炎症在肿瘤的生长与增殖中发挥着重要的作用,特别是炎症因子IL-1β、IL-8、TNF-α与肿瘤的发生、发展关系更为密切.炎症因子IL-1β、IL-8、TNF-α可通过改变肿瘤细胞的生存微环境,促进肿瘤新生血管生成,从而促进肿瘤细胞生长与增殖,同时也促进了肿瘤的转移,因此研究炎症因子(IL-1β、IL-8、TNF-α)与乳腺癌的关系具有重要意义.

  3. Relationship between Emotion, Severity of Illness and the Effect on IL-8 in Asthmatic Children%儿童情绪与哮喘病情的关系及对IL-8的影响

    Institute of Scientific and Technical Information of China (English)

    牛轶; 程自立; 王高华; 姜毅

    2002-01-01

    Objective: To examine the emotional states o f asthmatic children wit h different degrees of severity, as well as the effects of emotion on change of cytokines in airway. Methods: Asthmatic children were divi ded into two groups ac cording to the degrees of severity: moderate and mild. Their emotional states we re measured and results were compared. Correlation analysis was conducted betwee n scores on emotional scales and sputum levels of IL-8.Results: Total scores on anxiety and depression were higher in the moderate group than in the mild group. Negative correlation was found between levels of anxiety and IL-8 during acute exacerbation of asthmatic condition. Conclusion: Emotional distress was found to be increased with severity of asthmatic condition in children. Anxiety contribu ted to the decreased concentration of IL-8 in asthmatic children's airway.

  4. Staphylococcus epidermidis polysaccharide intercellular adhesin induces IL-8 expression in human astrocytes via a mechanism involving TLR2.

    LENUS (Irish Health Repository)

    Stevens, Niall T

    2009-03-01

    Staphylococcus epidermidis is an opportunistic biofilm-forming pathogen associated with neurosurgical device-related meningitis. Expression of the polysaccharide intercellular adhesin (PIA) on its surface promotes S. epidermidis biofilm formation. Here we investigated the pro-inflammatory properties of PIA against primary and transformed human astrocytes. PIA induced IL-8 expression in a dose- and\\/or time-dependent manner from U373 MG cells and primary normal human astrocytes. This effect was inhibited by depletion of N-acetyl-beta-d-glucosamine polymer from the PIA preparation with Lycopersicon esculentum lectin or sodium meta-periodate. Expression of dominant-negative versions of the TLR2 and TLR4 adaptor proteins MyD88 and Mal in U373 MG cells inhibited PIA-induced IL-8 production. Blocking IL-1 had no effect. PIA failed to induce IL-8 production from HEK293 cells stably expressing TLR4. However, in U373 MG cells which express TLR2, neutralization of TLR2 impaired PIA-induced IL-8 production. In addition to IL-8, PIA also induced expression of other cytokines from U373 MG cells including IL-6 and MCP-1. These data implicate PIA as an important immunogenic component of the S. epidermidis biofilm that can regulate pro-inflammatory cytokine production from human astrocytes, in part, via TLR2.

  5. TNFalpha and IL-8 regulate the expression and function of CD44 variant proteins in human colon carcinoma cells.

    Science.gov (United States)

    Barshishat, Michal; Ariel, Amiram; Cahalon, Liora; Chowers, Yehuda; Lider, Ofer; Schwartz, Betty

    2002-01-01

    The mechanisms underlying the inflammatory and metastatic processes share a number of similar pathways, such as those involving adhesion, migration and extravasation. In this article, the effects of pro-inflammatory cytokines on metastatic-related activities of colon cancer cells were tested. The expression and biological activity of the proteoglycan CD44 in low (LS174T) and high metastatic (HM7) cell lines following exposure to TNFalpha and IL-8 were assessed. Treated cells expressed more CD44 splice variants (CD44v), while CD44 standard protein (CD44s) expression remained unchanged. Treatment with TNFalpha induced IL-8 secretion and IL-8 gene transcription in a time-dependent manner. Both cytokines enhanced the ability of the cells to adhere to the CD44-specific ligand hyaluronic acid, an effect that was specifically blocked by an anti-IL-8 antibody. These results suggest that the effect of TNFalpha on IL-8 is responsible for the regulation of the expression of CD44 isoforms. Additional experiments showed that neither of the cytokines tested regulate the expression of CD44 gene regulation via activation of a well-characterized specific 22-bp epidermal growth factor regulatory element present in the CD44 promoter sequence, suggesting that this is not the mechanism of activation. We conclude that immuno-modulatory mediators can modify the expression of cell-to-cell or cell-to-matrix adhesion proteins, implicated in the determination of phenotypes associated with aggressiveness and metastasis of colon cancer cells. PMID:12090473

  6. Effect of Yinxieling decoction on PASI, TNF-α and IL-8 in patients with psoriasis vulgaris

    Institute of Scientific and Technical Information of China (English)

    Yong-Jiang Dai; Yu-Yang Li; Hui-Ming Zeng; Xiong-An Liang; Zhi-Jie Xie; Zhi-Ang Zheng; Qin-Hui Pan; Yi-Xiong Xing

    2014-01-01

    Objective:To study the effect ofYinxieling decoction onPASI,TNF-α andIL-8 in patients with psoriasis vulgaris. Methods:A total of120 cases of psoriasis vulgaris were divided into4 groups according to syndrome differentiation ofTCM and randomized controlled method: wind heat syndrome group(groupA), blood stasis syndrome group(groupB), blood dryness syndrome group (groupC) and control group(groupD)(n=30 per group).Patients in observation groups were treated withYinxieling decoction, while patients in control group were treated by placebo for8 weeks. Levels ofTNF-α andIL-8 were determined before treatment,4 and8 weeks after treatment. psoriasis area and severity index score was also performed before and after treatment.Results:psoriasis area and severity index score and serum level ofTNF-α,IL-8 were significantly decreased in all groups.The decrease in three observation groups was more significant(P<0.05 orP<0.01), and the decrease in wind heat syndrome group was the most significant(P<0.01). psoriasis area and severity index was positively correlated withTNF-α andIL-8, respectively (P<0.05).Conclusions:Yinxieling decoction has therapeutical effect on psoriasis vulgaris via regulatingTNF-α andIL-8.

  7. Enolase of Streptococcus Suis Serotype 2 Enhances Blood-Brain Barrier Permeability by Inducing IL-8 Release.

    Science.gov (United States)

    Sun, Yingying; Li, Na; Zhang, Jing; Liu, Hongtao; Liu, Jianfang; Xia, Xiaojing; Sun, Changjiang; Feng, Xin; Gu, Jingmin; Du, Chongtao; Han, Wenyu; Lei, Liancheng

    2016-04-01

    Streptococcus suis serotype 2 (SS2) is an emerging zoonosis, and meningitis is the most frequent clinical manifestation, but mechanism of its virulent factor, enolase (Eno), is unknown in meningitis. In this study, Eno was inducibly expressed and added to an in vitro Transwell co-culture model of the blood-brain barrier (BBB) consisted of porcine brain microvascular endothelial cells (PBMECs) and astrocytes (ACs), the results showed that Eno induces a significant increase in BBB permeability and promotes the release of IL-8 et al. cytokines. Furthermore, IL-8 could significantly destroy the integrity of the BBB model in vitro. In mice models administered Eno for 24 h, Eno could significantly promote Evans blue (EB) moving from the blood to the brain and significantly increased the serum and brain levels of IL-8, as detected by ELISA. While G31P (IL-8 receptor antagonist) significantly decreased the concentration of EB in the brains of mice injected with Eno. The present study demonstrated that SS2 Eno may play an important role in disrupting BBB integrity by prompting IL-8 release. PMID:26732390

  8. Clinical significance of determination of serum TNF, IL-8 and GM-CSF levels in pediatric patients with bronchial asthma

    International Nuclear Information System (INIS)

    Objective: To investigate the clinical significance of changes of serum TNF, IL-8 and GM-CSF in pediatric patients with bronchial asthma. Methods: Serum TNF, IL-8 and GM-CSF levels were measured with RIA in 32 pediatric patients with bronchial asthma and 30 controls. Results: Serum levels of TNF, IL-8 and GM-CSF were very significantly higher in pediatric patients with bronchial asthma than those in controls (P<0.01). After one week treatment, the levels dropped considerably but still remained significantly higher than those in controls (P<0.05). Conclusion: These cytokines participated in the pathogenesis of bronchial asthma. Monitoring the changes of their serum levels was helpful for the management of the diseases. (authors)

  9. The Expression of IL-6,IL-8 and TNF-αin Plasma of Breast Cancer Patients%乳腺癌患者血浆中IL-6、IL-8及TNF-α的表达

    Institute of Scientific and Technical Information of China (English)

    刘杨; 陈利琴; 王文斌; 缪文青; 黄明; 陈大平

    2016-01-01

    目的:探讨血浆中白细胞介素( IL)-6、IL-8及肿瘤坏死因子-α( TNF- a)与乳腺癌发生发展、临床分期及骨转移的关系。方法:111例乳腺肿瘤患者根据病理结果分为乳腺良性肿瘤组( n=50)、乳腺癌组( n=61),50例健康妇女作为正常对照组,采用酶联免疫吸附( ELISA)法分别检测3组患者血浆中IL-6、IL-8及TNF-α的水平,分析3项指标与乳腺癌临床分析、肿瘤转移以及年龄(≥50岁和<50岁)的关系。结果:乳腺癌组血浆IL-6、IL-8及TNF-α水平明显高于良性肿瘤组和正常对照组( P<0.05);随着乳腺癌临床分期的提高,IL-6、IL-8及TNF-α水平逐渐升高( P<0.05);乳腺癌骨转移患者血浆IL-6、IL-8及TNF-α水平明显高于乳腺癌无转移及乳腺癌其他脏器转移患者( P <0.05);年龄对乳腺癌患者血清 IL-6、IL-8及 TNF-α水平影响不大( P >0.05)。结论:血清IL-6、IL-8及TNF-α水平与乳腺癌的发生发展有关。%Objective:To discussthe relatiohship betweeh plasma ihterleukih(IL)-6,IL-8 ahd tumor hecrosis factor-α( TNF-α)ahd the developmeht,clihical stage ahd bohe metastasis of breast cahcer. Methods:Accordihg to the pathological results,111 cases of breast cahcer patiehtswere divided ihto behigh breast tumor group( n =50 ),breast cahcer group( n =61 ),50 healthy womeh as cohtrol group. Plasma IL-6,IL-8 ahd TNF-α levels of hormal cohtrol group,breast behigh tumor group ahd breast cahcer of 3 groups were measured by ehzyme-lihked immuhosorbeht( ELISA). Theh their cor-relatioh with clihical biological characteristics of breast cahcer was ahalyzed. Results:Plasma IL-6, IL-8 ahd TNF-α levels ih breast cahcer group were sighificahtly higher thah those ih behigh tumor group( P0 . 05 ). Conclusion:Plasma IL-6 ,IL-8 ahd TNF-αlevels may be associated with the developmeht of breast cahcer.

  10. Effects of remifentanil on TNF-α and IL-8 on lipopolysaccharide-induced acute lung injury in rabbits%瑞芬太尼对兔内毒素性急性肺损伤时TNF-α及IL-8的影响

    Institute of Scientific and Technical Information of China (English)

    周本昊; 杜成; 景亮; 刘晓甦

    2012-01-01

    Objective To investigate the effects of remifentanil on TNF - ctand IL - 8 on lipopolysaccharide - induced acute lung injury in rabbits. Methods Thirty healthy male New Zealand white rabbits weighing 2. 5 ~ 3. 5 kg were randomly divided into 5 groups( n = 6 each) : group I control (group C) ; group II ALI; group IH , IV, V low, median and high dose RF + LPS (group LR, MR, HR). The animals were anesthetized with intravenous 3% pentobarbital sodium 30 mg/kg, tracheostomized and mechanically ventilated. The carotid artery and j gular vein were cannulated for MAP and HR monitoring, blood sampling, and fluid and dr g administration. LPS 0. 5 mg/kg in 10 ml of normal saline(NS)was infused over 30 min in group II ~ V- Remifentanil 0. 2, 0. 4 or 0. 8 μg/(kg· min) was infused 15 min before LPS administration until the death of the animals. MAP, HR, peak airway pressure ( Ppeak ) , PaO2 and tumor necrosis factor ( TNF - a ) , interleukin - 8 ( IL - 8 ) concentration were measured immediately before LPS infusion (TO, baseline) and at 1,2. 5 and 5. 5 h after the end of LPS infusion. The animals were killed and the lungs were immediately removed for microscopic examination and determination of W/D lung weight ratio. Results MAP, HR and PaO2 were significantly decreased while W/D ratio and Ppeak were significantly increased after iv LPS infusion as compared with control group. LPS significantly increased plasma TNF - α and IL - 8 concentration and damaged the structure of lung tissue. Remifentanil infusion significantly attenuated the LPS -induced changes in a dose - dependent manner. Conclusion Remifentanil reduces LPS - induced acute lung injury in rabbits which is dose - dependent. The possible mechanism of protective effect is that by inhibiting the expression of TNF - α, IL - 8, remifentanil can inhibit neutrophilic granulocyte aggregation in lung, interfere with the cascade effect of inflammatory factor,and relieve the impairment of lung.%目的 探讨瑞芬太尼对

  11. Serum TNF-α, IL-8, VEGF Levels in Helicobacter pylori Infection and Their Association with Degree of Gastritis

    Directory of Open Access Journals (Sweden)

    Gontar A Siregar

    2015-04-01

    Full Text Available Aim: to investigate the serum levels of TNF-α, IL-8, VEGF in Helicobacter pylori infection, and their association with the degrees of gastritis histopathology. Methods: a cross-sectional study was done on 80 consecutive gastritis patients admitted to endoscopy units at Adam Malik General Hospital and Permata Bunda Hospital, Medan, Indonesia from July-December 2014. The Rapid Urease test was used for the diagnosis of H. pylori infection. The severity of chronic inflammation, neutrophil infiltration, atrophy, and intestinal metaplasia were assessed. Serum samples were obtained to determine circulating TNF-α, IL-8, and VEGF. Univariate and bivariate analysis (chi square, fisher’s exact, and mann-whitney test were done using SPSS version-22. Results: there were 41.25% of 80 patients infected with Helicobacter pylori. Serum TNF-α and VEGF levels in the infected group were significantly higher compared to H. pylori negative, but there were no significant differences between serum levels of IL-8 in H. pylori positive and negative. There were significant associations between serum level of TNF-α and IL-8 with degree of chronic inflammation, and also between serum level of IL-8 and degree of neutrophil infiltration. There were significant associations between serum level of VEGF and degree of atrophy, and also between serum level of VEGF and degree of intestinal metaplasia. Conclusion: High levels of TNF-α were associated with severe degree of chronic inflammation, high levels of IL-8 associated with severe degree of chronic inflammation and neutrophil infiltration, and high levels of VEGF associated with severe degree of premalignant gastric lesion. Key words: cytokine, neoangiogenesis, Helicobacter pylori, atrophic gastritis, intestinal metaplasia.

  12. IL-8、IL-17以及IL-18与胃癌的关系

    Institute of Scientific and Technical Information of China (English)

    林丹; 杜苗苗; 杜季梅

    2012-01-01

    胃癌是危害人类健康最常见的恶性肿瘤之一,其病死率仅次于肺癌,位居癌症死亡第2位。多项研究表明白细胞介素(interleukin,IL)IL-8、IL-17及IL-18,与胃癌的发生发展有着密切的联系。该文对IL-8、IL-17和IL-18与肿瘤和胃癌关系作一简要概述。

  13. Human astrocytes: secretome profiles of cytokines and chemokines.

    Directory of Open Access Journals (Sweden)

    Sung S Choi

    Full Text Available Astrocytes play a key role in maintenance of neuronal functions in the central nervous system by producing various cytokines, chemokines, and growth factors, which act as a molecular coordinator of neuron-glia communication. At the site of neuroinflammation, astrocyte-derived cytokines and chemokines play both neuroprotective and neurotoxic roles in brain lesions of human neurological diseases. At present, the comprehensive profile of human astrocyte-derived cytokines and chemokines during inflammation remains to be fully characterized. We investigated the cytokine secretome profile of highly purified human astrocytes by using a protein microarray. Non-stimulated human astrocytes in culture expressed eight cytokines, including G-CSF, GM-CSF, GROα (CXCL1, IL-6, IL-8 (CXCL8, MCP-1 (CCL2, MIF and Serpin E1. Following stimulation with IL-1β and TNF-α, activated astrocytes newly produced IL-1β, IL-1ra, TNF-α, IP-10 (CXCL10, MIP-1α (CCL3 and RANTES (CCL5, in addition to the induction of sICAM-1 and complement component 5. Database search indicated that most of cytokines and chemokines produced by non-stimulated and activated astrocytes are direct targets of the transcription factor NF-kB. These results indicated that cultured human astrocytes express a distinct set of NF-kB-target cytokines and chemokines in resting and activated conditions, suggesting that the NF-kB signaling pathway differentially regulates gene expression of cytokines and chemokines in human astrocytes under physiological and inflammatory conditions.

  14. Relationship and significance of the expression of COX-2 and IL-8 in breast cancer%乳腺癌组织中COX-2与IL-8表达的相关性及临床意义

    Institute of Scientific and Technical Information of China (English)

    陈守华; 张丽丽; 顾禾; 付荣湛

    2008-01-01

    目的:探讨乳腺癌组织中环氧化酶-2(COX-2)和白细胞介素-8(IL-8)表达的相关性及临床意义.方法:采用免疫组织化学法对60例乳腺癌患者病理组织中的COX-2和IL-8进行检测,并与31例乳腺良性疾病对照,分析其相关性,以及二者与肿瘤大小、浸润程度、TNM分期、淋巴结转移及雌激素受体(estrogen receptor,ER)和孕激素受体(progesteronreceptor,PR)表达等生物学行为的关系.结果:乳腺癌组织中COX-2和IL-8阳性表达率分别为66.7%、60.0%均显著高于对照组(P=0.000 6、P=0.000 2),且二者表达存在明显正相关(r=0.433,P0.05).结论:COX-2和IL-8在乳腺癌组织中过度表达且呈正相关,提示乳腺癌组织中COX-2和IL-8存在相互调控机制,共同促进肿瘤的发生和发展.

  15. The influence of adhesin protein from Aggregatibacter actinomycetemcomitans on IL-8 and MMP-8 titre in aggressive periodontitis

    Directory of Open Access Journals (Sweden)

    Rini Revijanti Ridwan

    2015-03-01

    Full Text Available Background: Adhesion can actually be considered as a part of both a powerful survival mechanism and a virulence mechanism for bacterial pathogens. Bacterial adhesin is an instrument for bacteria to do invasion to host. Bacterial adhesin depends on ligand interaction as a signaling mediator that will influence invasion and increase pro and anti-inflammatory because of the influence of the receptors of innate immune response. Aggregatibacter actimycetemcomitans has fimbriae included in type IV pili containing mostly with protein weighed 6.5 kDa and at least with protein weighed 54 kDa. Purpose: The purpose of this research is to analyze the influence of the induction of adhesin protein derived from A. actinomycetemcomitans on IL-8 and MMP-8 titre of Wistar rats. Methods: Adhesin protein derived from A. actinomycetemcomitans weighed 24 kDa was induced on the maxillary first molar sulcus of Wistar rats to prove that adhesin protein could affect IL-8 and MMP-8 titre. Next, to determine its influence, Elisa technique was conducted. Results: It is known that the levels of IL-8 and MMP-8 titre were increased in the group induced with adhesin protein derived from A. actinomycetemcomitans compared with the control group. Conclusion: It can be concluded that adhesin protein derived from A. actinomycetemcomitans can cause alveolar bone damage through the increasing levels of IL-8 and MMP-8 in aggressive periodontitis.

  16. Virodhamine and CP55,940 modulate cAMP production and IL-8 release in human bronchial epithelial cells

    NARCIS (Netherlands)

    Gkoumassi, E.; Dekkers, B. G. J.; Droege, M. J.; Elzinga, C. R. S.; Schmidt, M.; Meurs, H.; Zaagsma, J.; Nelemans, S. A.

    2007-01-01

    Background and purpose: We investigated expression of cannabinoid receptors and the effects of the endogenous cannabinoid virodhamine and the synthetic agonist CP55,940 on cAMP accumulation and interleukin-8 (IL-8) release in human bronchial epithelial cells. Experimental approach: Human bronchial e

  17. Finding ATF4/p75NTR/IL-8 Signal Pathway in Endothelial–Mesenchymal Transition by Safrole Oxide

    Science.gov (United States)

    Zhao, Wenbo; Yue, Hongwei; Su, Le; Zhang, ShangLi; Zhao, Jing

    2014-01-01

    Targeting the endothelial-to-mesenchymal transition (EndoMT) may be a novel therapeutic strategy for cancer and various diseases induced by fibrosis. We aimed to identify a small chemical molecule as an inducer of EndoMT and find a new signal pathway by using the inducer. Safrole oxide (SFO), 50 µg/ml, could most effectively induce EndoMT within 12 h. To understand the underlying molecular mechanism, we performed microarray, quantitative real-time PCR and western blot analysis to find key factors involved in SFO-induced EndoMT and demonstrated the involvement of the factors by RNAi. The expression of activating transcription factor 4 (ATF4), p75 neurotrophin receptor (p75NTR), and interleukin 8 (IL-8) was greatly increased in SFO-induced EndoMT. Knockdown of ATF4 inhibited the SFO-induced EndoMT completely, and knockdown of p75NTR or IL-8 partially inhibited the EndoMT, which suggests that all three factors were involved in the process. Furthermore, knockdown of p75NTR inhibited the SFO-increased IL-8 expression and secretion, and knockdown of ATF4 inhibited SFO-increased p75NTR level significantly. The ATF4/p75NTR/IL-8 signal pathway may have an important role in EndoMT induced by SFO. Our findings support potential novel targets for the therapeutics of cancer and fibrosis disease. PMID:24905361

  18. Finding ATF4/p75NTR/IL-8 signal pathway in endothelial-mesenchymal transition by safrole oxide.

    Directory of Open Access Journals (Sweden)

    Di Ge

    Full Text Available Targeting the endothelial-to-mesenchymal transition (EndoMT may be a novel therapeutic strategy for cancer and various diseases induced by fibrosis. We aimed to identify a small chemical molecule as an inducer of EndoMT and find a new signal pathway by using the inducer. Safrole oxide (SFO, 50 µg/ml, could most effectively induce EndoMT within 12 h. To understand the underlying molecular mechanism, we performed microarray, quantitative real-time PCR and western blot analysis to find key factors involved in SFO-induced EndoMT and demonstrated the involvement of the factors by RNAi. The expression of activating transcription factor 4 (ATF4, p75 neurotrophin receptor (p75NTR, and interleukin 8 (IL-8 was greatly increased in SFO-induced EndoMT. Knockdown of ATF4 inhibited the SFO-induced EndoMT completely, and knockdown of p75NTR or IL-8 partially inhibited the EndoMT, which suggests that all three factors were involved in the process. Furthermore, knockdown of p75NTR inhibited the SFO-increased IL-8 expression and secretion, and knockdown of ATF4 inhibited SFO-increased p75NTR level significantly. The ATF4/p75NTR/IL-8 signal pathway may have an important role in EndoMT induced by SFO. Our findings support potential novel targets for the therapeutics of cancer and fibrosis disease.

  19. Finding ATF4/p75NTR/IL-8 signal pathway in endothelial-mesenchymal transition by safrole oxide.

    Science.gov (United States)

    Ge, Di; Jing, Qingchuan; Zhao, Wenbo; Yue, Hongwei; Su, Le; Zhang, ShangLi; Zhao, Jing

    2014-01-01

    Targeting the endothelial-to-mesenchymal transition (EndoMT) may be a novel therapeutic strategy for cancer and various diseases induced by fibrosis. We aimed to identify a small chemical molecule as an inducer of EndoMT and find a new signal pathway by using the inducer. Safrole oxide (SFO), 50 µg/ml, could most effectively induce EndoMT within 12 h. To understand the underlying molecular mechanism, we performed microarray, quantitative real-time PCR and western blot analysis to find key factors involved in SFO-induced EndoMT and demonstrated the involvement of the factors by RNAi. The expression of activating transcription factor 4 (ATF4), p75 neurotrophin receptor (p75NTR), and interleukin 8 (IL-8) was greatly increased in SFO-induced EndoMT. Knockdown of ATF4 inhibited the SFO-induced EndoMT completely, and knockdown of p75NTR or IL-8 partially inhibited the EndoMT, which suggests that all three factors were involved in the process. Furthermore, knockdown of p75NTR inhibited the SFO-increased IL-8 expression and secretion, and knockdown of ATF4 inhibited SFO-increased p75NTR level significantly. The ATF4/p75NTR/IL-8 signal pathway may have an important role in EndoMT induced by SFO. Our findings support potential novel targets for the therapeutics of cancer and fibrosis disease.

  20. Effects of ulinastatin and docataxel on breast tumor growth and expression of IL-6, IL-8, and TNF-α

    Directory of Open Access Journals (Sweden)

    Luo Jie

    2011-02-01

    Full Text Available Abstract Objective This study investigated the effects of Ulinastatin (UTI and docataxel (Taxotere, TAX on tumor growth and expression of interleukin-6 (IL-6, interleukin-8 (IL-8, and tumor necrosis factor-α (TNF-α in breast cancer. Methods MDA-MB-231 human breast carcinoma cells were cultured in vitro and injected into nude mice to establish breast tumor xenografts in vivo. Cultured cells and mice with tumors were randomly divided into four groups for treatment with TAX, UTI, and TAX+UTI. The effects of these drug treatments on cell proliferation and apoptosis was measured using the MTT assay and the Annexin V/propidium iodide (PI double-staining method, respectively. IL-6, IL-8, and TNF-α expression levels were determined by measuring mRNA transcripts in cultured cells by RT-PCR and cytokine proteins in solid tumors using immunohistochemistry. Results UTI, TAX, and UTI+TAX inhibited the growth of MDA-MB-231 cells in vitro and tumors in vivo. These two drugs, particularly when used in combination, promote tumor cell apoptosis and down-regulate the expression IL-6, IL-8, and TNF-α cytokines. Conclusion Both UTI and TAX inhibited the growth of MDA-MB-231 breast carcinoma cells. UTI enhanced the inhibitory effect of TAX by a mechanism consistent with the down-regulated expression of IL-6, IL-8, and TNF-α.

  1. The predictive value of interleukin-8 (IL-8) in hospitalised patients with fever and chemotherapy-induced neutropenia

    NARCIS (Netherlands)

    Tromp, Yvonne H.; Daenen, Simon M. G. J.; Sluiter, Wim J.; Vellenga, Edo

    2009-01-01

    Aim: To demonstrate whether serum Interleukin-8 (IL-8) is a relevant parameter to select hospitalised patients with chemotherapy-induced neutropenic fever with low or high probability of infection. Results: 90 assessable febrile episodes in 73 patients were evaluated; 46% of the febrile episodes wer

  2. Immunologic changes in TNF-alpha, sE-selectin, sP-selectin, sICAM-1, and IL-8 in pediatric patients treated for psoriasis with the Goeckerman regimen

    Energy Technology Data Exchange (ETDEWEB)

    Borska, L.; Fiala, Z.; Krejsek, J.; Andrys, C.; Vokurkova, D.; Hamakova, K.; Kremlacek, J.; Ettler, K. [Charles University of Prague, Hradec Kralove (Czech Republic). Faculty of Medicine

    2007-11-15

    Psoriasis is a chronic inflammatory skin disease which is often manifested during childhood. The present study investigated changes in the serum levels of proinflammatory cytokines and soluble forms of adhesion molecules in children with psoriasis. The observed patient group of 26 children was treated with the Goeckerman regimen. This therapy combines dermal application of crude coal tar with ultraviolet radiation. The Psoriasis Area Severity Index decreased significantly after treatment by with the Goeckerman regimen (p < 0.001). Serum levels of the proinflammatory cytokine TNF-alpha and adhesion molecules sICAM-1, sP-selectin and sE-selectin decreased after the Goeckerman regimen. The TNF-alpha and sICAM-1 decreased significantly (p < 0.05). Our findings support the complex role of these immune parameters in the immunopathogenesis of psoriasis in children. The serum level of IL-8 increased after the Goeckerman regimen. This fact indicates that the chemokine pathway of IL-8 activity could be modulated by this treatment, most likely by polycyclic aromatic hydrocarbons.

  3. Chemokine Receptors and Transplantation

    Institute of Scientific and Technical Information of China (English)

    Jinquan Tan; Gang Zhou

    2005-01-01

    A complex process including both the innate and acquired immune responses results in allograft rejection. Some chemokine receptors and their ligands play essential roles not only for leukocyte migration into the graft but also in facilitating dendritic and T cell trafficking between lymph nodes and the transplant in the early and late stage of the allogeneic response. This review focuses on the impact of these chemoattractant proteins on transplant outcome and novel diagnostic and therapeutic approaches for antirejection therapy based on targeting of chemokine receptors and/or their ligands. Cellular & Molecular Immunology.

  4. 新生儿败血症血清IL-6、IL-8、PCT检测及其临床意义

    Institute of Scientific and Technical Information of China (English)

    胡新民; 徐美玉; 蒋晓天

    2002-01-01

    目的:探讨新生儿败血症时血清IL-6、IL-8、PCT的变化.方法:IL-6、IL-8用ELISA双夹心法,PCT用放射免疫法.结果:新生儿败血症血清IL-6、IL-8、PCT明显升高.结论:IL~6、IL-8、PCT可作为新生儿败血症的早期诊断指标.

  5. Effects of recombinant human interleukin-8 (rhIL-8) on the bone marrow cells of normal BALB/c mice

    International Nuclear Information System (INIS)

    Objective: To observe the colony formation ability of recombinant human interleukin-8 (rhIL-8) on bone marrow cells (BMCs) of normal mice in vivo. Methods: By means of cells culture and flow cytometry (FCM), the colony-stimulating activity of rhIL-8 on BMCs of normal mice was studied. Results: The experimental studies in vivo demonstrated that rhIL-8 could not changed the counts of CFU-GM and distribution of cell cycle in BMCs. Conclusion: rhIL-8 has no colony-stimulating activity to BMCs of normal mice

  6. Clinical significance of determination of changes of serum GM-CSF, IL-8, IL-6 levels after treatment in pediatric patients with bronchial asthma

    International Nuclear Information System (INIS)

    Objective: To investigate the changes of serum GM-CSF, IL-8 and IL-6 levels both before and after treatment in pediatric patients with bronchial asthma. Methods: Serum GM-CSF, IL-8 and IL-6 levels were measured with RIA in 32 pediatric patients with bronchial asthma both before and after treatment as well as in 30 controls. Results: Before treatment, the serum GM-CSF, IL-8, IL-6 levels were significantly higher in the patients than those in the controls (P0.05). Conclusion: Abnormal high serum GM-CSF, IL-8, IL-6 levels played important role in the pathogenesis of bronchial asthma in children. (authors)

  7. Effects of long-term smoking on expression of IL-8 and E-selectin in rat lungs%长期吸烟对大鼠肺E-选择素和IL-8表达影响

    Institute of Scientific and Technical Information of China (English)

    万丹; 李文芳; 石梦蝶; 刘福荣

    2011-01-01

    目的 探讨长期吸烟对大鼠的肺损伤及相关炎性因子表达的影响.方法 56只雄性SD大鼠,随机分为对照组和低、中、高3个剂量吸烟组,采用自主开发的吸烟机给烟12周;放免法检测支气管肺灌洗液(BALF)中白介素-8(IL-8)的含量,免疫组化法检测肺血管内皮细胞E-选择素的表达水平.结果 高、中、低剂量吸烟组大鼠BALF中IL-8的含量分别为(0.77±0.010)、(0.71±0.171)、(0.62±0.088)ng/mL,高于对照组(0.28±0.133))ng/mL,差异有统计学意义(p<0.01);高、中、低剂量吸烟组E-选择素的表达分别为(0.27±0.030)、(0.18±0.034)、(0.16±0.025),均高于对照组(0.07±0.023),差异有统计学意义(P<0.01);中剂量吸烟组肺血管内皮细胞E-选择素与BALF中IL-8的含量呈明显正相关(r=0.716,P<0.01).结论 长期吸烟导致气道炎症介质IL-8和E-选择素的表达升高,促进气道内炎症反应,对支气管肺组织造成严重损害.%Objective To investigate the influence of long-term smoking on the expression of inflammatory factors in rat lung tissue. Methods Fifty-six male SD rats were randomly divided into four groups:control, low-, moderate-, and highdose group. The rats in each group were exposed to cigarette smoke at different dose for 12 weeks. The level of interleukin-8 (IL-8) in bronchoalveolar lavage fluid (BALF) was measured with radioimmunoassay. Immunohistochemistry assay was carried out to examine the expression of E-selectin in lung tissue. Results The levels of IL-8 in BALF increased significantly in high-,moderate-,and low-dose group(0. 77 ±0.010,0. 71 ±0. 171 ,and 0. 62 ± 0. 088,respectively) compared to that of the control group(0. 28 ± 0. 133, P < 0. 01 ). The expression of E-selectin in pulmonary vascular increased significantly in high- , moderate- , and low-dose group(0. 27 ±0. 030,0. 18 ±0. 034,and 0. 16 ±0. 025,respectively) compared to that of the control group (0. 07 ± 0. 023,P < 0. 01 ). The level of IL-8

  8. IL-8 mRNA 定量检测在活动性结核病鉴别诊断中的价值%Diagnostic value of IL-8 mRNA in the differential diagnosis of active tuberculosis

    Institute of Scientific and Technical Information of China (English)

    曹志红; 曹彦; 程小星

    2015-01-01

    Objective To compare the mRNA expression of IL-8 from PBMCs stimulated with Mtb-specific antigens between pulmonary tuberculosis patients with latent tuberculosis infection (LTBI) and non-tuberculosis in-fection healthy controls. Methods The mRNA expression of IL-8 from PBMCs stimulated with Mtb-specific antigens was quantitatively detected by quantitative real-time PCR (qPCR). Receiver-operating-characteristic (ROC) curve was used to determine the cutoff points yielding the highest specificity and sensitivity, and discriminative ability was evaluated by the area under the ROC curve. Results The mRNA expression of IL-8 in tuberculosis patients was sig-nificantly higher than that in LTBI patients and healthy controls (P 3. 985) to identify active infection was 0. 72, with 54. 17% of sensitivity and 90% of specificity. The positive re-sult likelihood ratio was 5. 42, and 64. 7% of the cases were correctly classified. Conclusion The expression of IL-8 can be used as a biomarker for distinguishing between latent tuberculosis infection and active infection.%目的:研究活动性肺结核患者外周血单个核细胞(PBMCs)经结核特异性抗原刺激后白介素-8(interleukin-8,IL-8)的 mRNA 表达情况并与结核潜伏感染(latent tuberculosis infection,LTBI)及非结核感染健康对照组进行比较。方法提取研究对象的 PBMCs,经特异性抗原肽刺激后,收集细胞并提取总 RNA 然后经实时荧光定量 PCR 检测技术比较各组 IL-8 mRNA 表达情况。然后以敏感性(sensitivity)为纵坐标,1-特异性(1-specificity)为横坐标绘制结核组和 LTBI 组相比较的 ROC 曲线。结果经结核特异性抗原刺激后,结核组PBMCs 中 IL-8基因 mRNA 的相对表达量明显高于 LTBI 和健康对照组,差异有统计学意义(P <0.05)。 ROC曲线下面积为0.72。以3.985为临界值,鉴别活动性结核病和 LTBI 的敏感性和特异性分别为54.17%和90.00%,此时阳性似然比等于5.42,64.7%的

  9. Chemokines and Chemokine Receptors in the Development of Lupus Nephritis

    Directory of Open Access Journals (Sweden)

    Xiaofeng Liao

    2016-01-01

    Full Text Available Lupus nephritis (LN is a major cause of morbidity and mortality in the patients with systemic lupus erythematosus (SLE, an autoimmune disease with damage to multiple organs. Leukocyte recruitment into the inflamed kidney is a critical step to promote LN progression, and the chemokine/chemokine receptor system is necessary for leukocyte recruitment. In this review, we summarize recent studies on the roles of chemokines and chemokine receptors in the development of LN and discuss the potential and hurdles of developing novel, chemokine-based drugs to treat LN.

  10. Chemokines and Chemokine Receptors in the Development of Lupus Nephritis.

    Science.gov (United States)

    Liao, Xiaofeng; Pirapakaran, Tharshikha; Luo, Xin M

    2016-01-01

    Lupus nephritis (LN) is a major cause of morbidity and mortality in the patients with systemic lupus erythematosus (SLE), an autoimmune disease with damage to multiple organs. Leukocyte recruitment into the inflamed kidney is a critical step to promote LN progression, and the chemokine/chemokine receptor system is necessary for leukocyte recruitment. In this review, we summarize recent studies on the roles of chemokines and chemokine receptors in the development of LN and discuss the potential and hurdles of developing novel, chemokine-based drugs to treat LN. PMID:27403037

  11. Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-κB in immortalized and malignant oral keratinocytes

    Directory of Open Access Journals (Sweden)

    Lee Suk-Keun

    2007-09-01

    Full Text Available Abstract Background Interleukin-8 (IL-8 is a cytokine that plays an important role in tumor progression in a variety of cancer types; however, its regulation is not well understood in oral cancer cells. In the present study, we examined the expression and mechanism of IL-8 in which it is involved by treating immortalized (IHOK and malignant human oral keratinocytes (HN12 cells with deferoxamine (DFO. Methods IL-8 production was measured by an enzyme-linked immunoabsorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR analysis. Electrophoretic mobility shift assays was used to determine NF-κB binding activity. Phosphorylation and degradation of the I-κB were analyized by Western blot. Results IHOK cells incubated with DFO showed increased expression of IL-8 mRNA, as well as higher release of the IL-8 protein. The up-regulation of DFO-induced IL-8 expression was higher in IHOK cells than in HN12 cells and was concentration-dependent. DFO acted additively with IL-1β to strongly up-regulate IL-8 in IHOK cells but not in HN12 cells. Accordingly, selective p38 and ERK1/2 inhibitors for both kinases abolished DFO-induced IL-8 expression in both IHOK and HN12 cells. Furthermore, DFO induced the degradation and phosphorylation of IκB, and activation of NF-κB. The IL-8 inducing effects of DFO were mediated by a nitric oxide donor (S-nitrosoglutathione, and by pyrrolidine dithiocarbamate, an inhibitor of NF-κB, as well as by wortmannin, which inhibits the phosphatidylinositol 3-kinase-dependent activation of NAD(PH oxidase. Conclusion This results demonstrate that DFO-induced IL-8 acts via multiple signaling pathways in immortalized and malignant oral keratinocytes, and that the control of IL-8 may be an important target for immunotheraphy against human oral premalignant lesions.

  12. Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-κB in immortalized and malignant oral keratinocytes

    International Nuclear Information System (INIS)

    Interleukin-8 (IL-8) is a cytokine that plays an important role in tumor progression in a variety of cancer types; however, its regulation is not well understood in oral cancer cells. In the present study, we examined the expression and mechanism of IL-8 in which it is involved by treating immortalized (IHOK) and malignant human oral keratinocytes (HN12) cells with deferoxamine (DFO). IL-8 production was measured by an enzyme-linked immunoabsorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Electrophoretic mobility shift assays was used to determine NF-κB binding activity. Phosphorylation and degradation of the I-κB were analyized by Western blot. IHOK cells incubated with DFO showed increased expression of IL-8 mRNA, as well as higher release of the IL-8 protein. The up-regulation of DFO-induced IL-8 expression was higher in IHOK cells than in HN12 cells and was concentration-dependent. DFO acted additively with IL-1β to strongly up-regulate IL-8 in IHOK cells but not in HN12 cells. Accordingly, selective p38 and ERK1/2 inhibitors for both kinases abolished DFO-induced IL-8 expression in both IHOK and HN12 cells. Furthermore, DFO induced the degradation and phosphorylation of IκB, and activation of NF-κB. The IL-8 inducing effects of DFO were mediated by a nitric oxide donor (S-nitrosoglutathione), and by pyrrolidine dithiocarbamate, an inhibitor of NF-κB, as well as by wortmannin, which inhibits the phosphatidylinositol 3-kinase-dependent activation of NAD(P)H oxidase. This results demonstrate that DFO-induced IL-8 acts via multiple signaling pathways in immortalized and malignant oral keratinocytes, and that the control of IL-8 may be an important target for immunotheraphy against human oral premalignant lesions

  13. IL-6和IL-8在三氯乙烯致敏豚鼠血清中的变化%Variation of IL-6 and IL-8 levels in serum of guinea pigs sensitized by trichloroethylene

    Institute of Scientific and Technical Information of China (English)

    汪亮; 汪立杰; 戴丹; 沈彤; 朱启星

    2010-01-01

    目的 通过豚鼠致敏最大值试验(guinea pig maximization teat,GPMT)方法建立豚鼠致敏模型,检测并比较TCE致敏豚鼠与未致敏豚鼠血清中IL-6和IL-8的水平,探讨IL-6和IL-8在三氯乙烯(TCE)过敏性皮炎中的作用.方法 将豚鼠随机分为空白对照组,溶剂(橄榄油)对照组,DNCB阳性对照组和TCE处理组.采用GPMT法建立豚鼠致敏模型.根据致敏结果及末次激发后采血的不同时点将TCE处理组分为TCE未致敏24 h组,TCE致敏24 h组.TCE未致敏72 h组,TCE致敏72 h组.用ELISA试剂盒测定血清中IL-6和IL-8的含量.结果 DNCB组致敏率为100%,TCE组致敏率为62.1%.溶剂对照组与空白对照组差异均无统计学意义.与溶剂对照组相比,TCE未致敏24 h组IL-6水平降低,差异有统计学意义(P<0.05),TCE未致敏72 h组与TCE未致敏24 h组相比,IL-6水平明显升高,差异有统计学意义(P<0.05).与溶剂对照组相比,TCE未致敏72组IL-8水平明显降低,差异有统计学意义(P<0.05).结论 血清中细胞因子IL-6和IL-8水平在TCE诱导的致敏组和未致敏组豚鼠间,仅个别时间段的差异有统计学意义,提示两者可能仅在一定时间段中发挥作用.

  14. Down-regulation of IL-8 expression in human airway epithelial cells through helper-dependent adenoviral-mediated RNA interference

    Institute of Scientific and Technical Information of China (English)

    Huibi CAO; Anan WANG; Bernard MARTIN; David R.KOEHLER; Pamela L.ZEITLIN; A.Keith TANAWELL; Jim HU

    2005-01-01

    Interleukin (IL)-8 is a potent neutrophil chemotactic factor and a crucial mediator in neutrophil-dependent inflammation.Various cell types produce IL-8, either in response to external stimuli such as cytokines or bacterial infection, or after malignant transformation. Anti-IL-8 strategies have been considered for anti-inflammatory therapy. In this paper we demonstrate that the RNA interference technique can be used to efficiently down-regulate IL-8 protein expression in airway epithelial cells. We used a helper-dependent adenoviral vector to express a small hairpin (sh)RNA targeting human IL-8 in cultured airway epithelial cells (IB3-1, Cftr-/-; C38, Cftr-corrected) stimulated with TNF-α, IL-1 β or heat-inactivated Burkholderia cenocepacia. Stimulated IL-8 expression in IB3-1 and C38 cells was significantly reduced by shRNA expression. The shRNA targeting IL-8 had no effect on the activation of NF-κB, or on the protein levels of Iκ B or IL-6, suggesting that this anti-IL-8 strategy was highly specific, and therefore may offer potential for the treatment of inflammatory diseases.

  15. Clinical Value of IL-6 and IL-8 in Serum of Cases with Breast Cancer%乳腺癌患者血清中IL-6和IL-8测定的临床价值

    Institute of Scientific and Technical Information of China (English)

    李明; 张金业; 林兰; 刘继斌

    2011-01-01

    Objective To investigate a new attempt on serological diagnosis of breast cancer. Methods The serum IL-6 and IL-8 in 60 cases with breast cancer,30 cases of benign disease,and 40 healthy controls were tested by using ELISA method. Results There were significantly different among control group,benign breast and breast cancer group. There were a certain relationship between serum IL-6 and IL-8 and staging and prognosis in breast cancer. Conclusion IL-6 and IL-8 may be involved in breast cancer occurrence and development of the whole process. It could reflect changes in the biological behavior and prognosis of breast cancer,their monitoring has important clinical significance.%目的 为乳腺癌诊断提供血清学新尝试.方法 60例乳腺癌患者均来自于2009年3月~2010年3月南通市肿瘤医院病例,均为女性,年龄27~78岁,平均年龄57岁.所有患者均经手术病理证实且术前未经过化疗、放疗、内分泌及生物治疗.乳腺良性患者女性30例,年龄21~63岁,平均年龄36岁.对照组:健康体检者女性40例,年龄19~47岁,平均年龄33岁.所有研究对象近半年内未服用过免疫调节剂和激素类药物.采用酶联免疫吸附(ELISA)方法检测乳腺癌患者血清中IL-6和IL-8.结果 对照组、乳腺良性患者组以及乳腺癌组三者之间差异有统计学显著性意义(P<0.05);乳腺癌血清IL-6和IL-8水平与分期以及预后有一定的关系(P<0.05).结论 IL-6和IL-8可能参与了乳腺癌发生、发展的全过程,它的变化可间接反映乳腺癌的生物学行为和预后,对其监测具有重要的临床意义.

  16. Teleost Chemokines and Their Receptors

    Directory of Open Access Journals (Sweden)

    Steve Bird

    2015-11-01

    Full Text Available Chemokines are a superfamily of cytokines that appeared about 650 million years ago, at the emergence of vertebrates, and are responsible for regulating cell migration under both inflammatory and physiological conditions. The first teleost chemokine gene was reported in rainbow trout in 1998. Since then, numerous chemokine genes have been identified in diverse fish species evidencing the great differences that exist among fish and mammalian chemokines, and within the different fish species, as a consequence of extensive intrachromosomal gene duplications and different infectious experiences. Subsequently, it has only been possible to establish clear homologies with mammalian chemokines in the case of some chemokines with well-conserved homeostatic roles, whereas the functionality of other chemokine genes will have to be independently addressed in each species. Despite this, functional studies have only been undertaken for a few of these chemokine genes. In this review, we describe the current state of knowledge of chemokine biology in teleost fish. We have mainly focused on those species for which more research efforts have been made in this subject, specially zebrafish (Danio rerio, rainbow trout (Oncorhynchus mykiss and catfish (Ictalurus punctatus, outlining which genes have been identified thus far, highlighting the most important aspects of their expression regulation and addressing any known aspects of their biological role in immunity. Finally, we summarise what is known about the chemokine receptors in teleosts and provide some analysis using recently available data to help characterise them more clearly.

  17. Detection and significance of IL-8, CD11b in renal tissues of proliferative glomerulo-nephritis%增殖性肾小球肾炎肾组织IL-8、CD11b检测及意义

    Institute of Scientific and Technical Information of China (English)

    薛超; 朱妙珍

    2001-01-01

    @@白细胞介素-8(Interleukin-8,IL-8)在炎症癖动和维持中具重要意义[1]。本研究采用免疫组化方法检测了增殖性肾小球肾炎(Proliferative glomerulonephritis,PGN)肾组织中IL-8及中性粒细胞相关抗原(CD11b),以无增殖性发变的正常人及膜性肾病(Membraneous nephropathy,MN)患者肾组织的检测作对照,探讨IL-8及其介导的炎症症状在PGN肾组织的表现及意义。 1 材料和方法 病变肾组织来自重庆大坪医院肾内科1997-07-1998-03住院治疗并行肾穿刺活检的17例PGN患者,其中男性8例,女性9例,年龄11~69岁。包括非IgA系膜增殖性肾炎11例。8例男性肾移植供肾作正常对照组。7例MN作第二对照组,其中男性3例,女性4例,年龄16~60岁。 免疫组织化学:采用小鼠抗人IL-8单抗(第四军医大学免疫教研室)、小鼠抗人CD11b单抗(北京邦定公司);二抗、三抗采用S-P试剂盒(北京邦定公司);DAB显色。

  18. Follicular Proinflammatory Cytokines and Chemokines as Markers of IVF Success

    Directory of Open Access Journals (Sweden)

    Aili Sarapik

    2012-01-01

    Full Text Available Cytokines are key modulators of the immune system and also contribute to regulation of the ovarian cycle. In this study, Bender MedSystems FlowCytomix technology was used to analyze follicular cytokines (proinflammatory: IL-1β, IL-6, IL-18, IFN-γ, IFN-α, TNF-α, IL-12, and IL-23;, and anti-inflammatory: G-CSF, chemokines (MIP-1α, MIP-1β, MCP-1, RANTES, and IL-8, and other biomarkers (sAPO-1/Fas, CD44(v6 in 153 women undergoing in vitro fertilization (IVF. Cytokine origin was studied by mRNA analysis of granulosa cells. Higher follicular MIP-1α and CD44(v6 were found to correlate with polycystic ovary syndrome, IL-23, INF-γ, and TNF-α with endometriosis, higher CD44(v6 but lower IL-β and INF-α correlated with tubal factor infertility, and lower levels of IL-18 and CD44(v6 characterized unexplained infertility. IL-12 positively correlated with oocyte fertilization and embryo development, while increased IL-18, IL-8, and MIP-1β were associated with successful IVF-induced pregnancy.

  19. Impact of endoscopically minimal involvement on IL-8 mRnA expression in esophageal mucosa of Patients with non-erosive reflux disease

    Institute of Scientific and Technical Information of China (English)

    Yusei Kanazawa; Ikuo Murata; Shunichi Yamashita; Shigeru Kohno; Hajime Isomoto; Chun-Yang Wen; Ai-Ping Wang; Vladimir A Saenko; Akira Ohtsuru; Fuminao Takeshima; Katsuhisa Omagari; Yohei Mizuta

    2003-01-01

    AIM: Little has been known about the pathogenesis of nonerosive reflux disease (NERD). Recent studies have implicated interleukin 8 (IL-8) in the development and progression of gastroesophgeal reflux disease (GERD). The purpose of this study was to determine IL-8 RNA expression levels in NERD patients with or without subtle mucosal changes.METHODS: We studied 26 patients with NERD and 13 asymptomatic controls. Biopsy sample was taken from the esophagus 3 cm above the gastroesophageal junction and snap frozen for measurement of IL-8 mRNA levels by real-time quantitative polyrnerase chain reaction (PCR). We also examined mRNA expression of IL-8 receptors, CXCR-1 and -2 by reverse transcriptase PCR. The patients were endoscopically classified into grade M (mucosal color changes without visible mucosal break) and N (neither minimal involvement nor mucosal break) of the modified Los Angeles classification.RESULTS: The relative IL-8 mRNA expression levels were significantly higher in esophageal mucosa of NERD patients than those in esophageal mucosa of the controls. There was a significant difference in IL-8 mRNA levels between grades M and N. The CXCR-1 and -2 mRNAs were constitutively expressed in esophageal mucosa.CONCLUSION: Our results suggest that high IL-8 levels in esophageal mucosa may be involved in the pathogenesis of NERD through interaction with its receptors. NERD seems to be composed of a heterogeneous population in terms of not only endoscopically minimal involvement but also immune and inflammatory processes.

  20. IL-8及其受体在大肠癌细胞中的表达、功能及相互作用

    Institute of Scientific and Technical Information of China (English)

    赵之; 李芳

    2011-01-01

    IL-8在人体正常细胞中不表达,但在许多恶性肿瘤细胞中高表达,其中包含大肠癌。IL-8与细胞表面G-蛋白偶联受体(CXCRl/CXCR2)结合,促进肿瘤细胞生长、血管形成和转移,通过丝氨酸-苏氨酸激酶激活,蛋白酪氨酸激酶(PTK)活化,Rho-乌苷三磷酸酶(Rho—GTPases)活化等特异信号传导途径成为肿瘤微环境重要调节因子。IL-8受体使表皮生长因子受体(EGFR)配体脱落,激活EGFR参与CXCRl和CXCR2活化过程,正调节IL-8产物,诱导IL-8的表达,并发出促细胞生长信号,促进肿瘤生长、血管生成等。本文对IL-8IL-8受体CXCl/2在大肠癌的高表达以及对肿瘤生物学的影响进行综述。

  1. Genetic and physical mapping of 2q35 in the region of NRAMP and IL8R genes: Identification of a polymorphic repeat in exon 2 of NRAMP

    Energy Technology Data Exchange (ETDEWEB)

    White, J.K.; Shaw, M.A.; Barton, C.H. [Addenbrooke`s Hospital, Cambridge (United Kingdom)] [and others

    1994-11-15

    Recent interest has focused on the region of conserved synteny between mouse chromosome 1 and human 2q33-q37, particularly over the region encoding the murine macrophage resistance gene Ity/Lsh/Bcg (candidate Nramp) and members of the Il8r interleukin-8 (IL8) receptor gene cluster. In this paper, identification of a restriction fragment length polymorphism in the Il8RB gene in 35 pedigrees previously typed for markers in the 2q33-37 interval provided evidence (lod scores > 3) for linkage between Il8RB and the 2q34-135 markers FN1, TNP1, VIL1, and DES. Physical mapping, using yeast artificial chromosomes isolated with VIL1, confirmed that IL8RA, IL8RB and the IL8RB pseudogene map within the NRAMP-VIL1 interval, with the physical distance (155 kb) from 5{prime} LSH to 3{prime} VIL1 representing {approx}3-fold that observed in the mouse. Partial sequencing of NRAMP confirmed the presence of the N-terminal proline/serine-rich putative SH3 binding domain in exon 2 of the human gene. Further analysis of Brazilian leprosy and visceral leishmaniasis pedigrees identified a rare second allele varying in a 9-nucleotide repeat motif of the exon 2 sequence but segregating independently of the disease phenotype. 38 refs., 4 figs., 3 tabs.

  2. Elevated CXC chemokines in urine noninvasively discriminate OAB from UTI.

    Science.gov (United States)

    Tyagi, Pradeep; Tyagi, Vikas; Qu, Xianggui; Chuang, Yao Chi; Kuo, Hann-Chorng; Chancellor, Michael

    2016-09-01

    Overlapping symptoms of overactive bladder (OAB) and urinary tract infection (UTI) often complicate the diagnosis and contribute to overprescription of antibiotics. Inflammatory response is a shared characteristic of both UTI and OAB and here we hypothesized that molecular differences in inflammatory response seen in urine can help discriminate OAB from UTI. Subjects in the age range of (20-88 yr) of either sex were recruited for this urine analysis study. Urine specimens were available from 62 UTI patients with positive dipstick test before antibiotic treatment. Six of these patients also provided urine after completion of antibiotic treatment. Subjects in cohorts of OAB (n = 59) and asymptomatic controls (n = 26) were negative for dipstick test. Urinary chemokines were measured by MILLIPLEX MAP Human Cytokine/Chemokine Immunoassay and their association with UTI and OAB was determined by univariate and multivariate statistics. Significant elevation of CXCL-1, CXCL-8 (IL-8), and CXCL-10 together with reduced levels for a receptor antagonist of IL-1A (sIL-1RA) were seen in UTI relative to OAB and asymptomatic controls. Elevated CXCL-1 urine levels predicted UTI with odds ratio of 1.018 and showed a specificity of 80.77% and sensitivity of 59.68%. Postantibiotic treatment, reduction was seen in all CXC chemokines with a significant reduction for CXCL-10. Strong association of CXCL-1 and CXCL-10 for UTI over OAB indicates mechanistic differences in signaling pathways driving inflammation secondary of infection in UTI compared with a lack of infection in OAB. Urinary chemokines highlight molecular differences in the paracrine signaling driving the overlapping symptoms of UTI and OAB.

  3. Elevated CXC chemokines in urine noninvasively discriminate OAB from UTI.

    Science.gov (United States)

    Tyagi, Pradeep; Tyagi, Vikas; Qu, Xianggui; Chuang, Yao Chi; Kuo, Hann-Chorng; Chancellor, Michael

    2016-09-01

    Overlapping symptoms of overactive bladder (OAB) and urinary tract infection (UTI) often complicate the diagnosis and contribute to overprescription of antibiotics. Inflammatory response is a shared characteristic of both UTI and OAB and here we hypothesized that molecular differences in inflammatory response seen in urine can help discriminate OAB from UTI. Subjects in the age range of (20-88 yr) of either sex were recruited for this urine analysis study. Urine specimens were available from 62 UTI patients with positive dipstick test before antibiotic treatment. Six of these patients also provided urine after completion of antibiotic treatment. Subjects in cohorts of OAB (n = 59) and asymptomatic controls (n = 26) were negative for dipstick test. Urinary chemokines were measured by MILLIPLEX MAP Human Cytokine/Chemokine Immunoassay and their association with UTI and OAB was determined by univariate and multivariate statistics. Significant elevation of CXCL-1, CXCL-8 (IL-8), and CXCL-10 together with reduced levels for a receptor antagonist of IL-1A (sIL-1RA) were seen in UTI relative to OAB and asymptomatic controls. Elevated CXCL-1 urine levels predicted UTI with odds ratio of 1.018 and showed a specificity of 80.77% and sensitivity of 59.68%. Postantibiotic treatment, reduction was seen in all CXC chemokines with a significant reduction for CXCL-10. Strong association of CXCL-1 and CXCL-10 for UTI over OAB indicates mechanistic differences in signaling pathways driving inflammation secondary of infection in UTI compared with a lack of infection in OAB. Urinary chemokines highlight molecular differences in the paracrine signaling driving the overlapping symptoms of UTI and OAB. PMID:27335375

  4. Cerebrospinal fluid IL-12p40, CXCL13 and IL-8 as a combinatorial biomarker of active intrathecal inflammation.

    Directory of Open Access Journals (Sweden)

    Bibiana Bielekova

    Full Text Available Diagnosis and management of the neuroinflammatory diseases of the central nervous system (CNS are hindered by the lack of reliable biomarkers of active intrathecal inflammation. We hypothesized that measuring several putative inflammatory biomarkers simultaneously will augment specificity and sensitivity of the biomarker to the clinically useful range. Based on our pilot experiment in which we measured 18 inflammatory biomarkers in 10-fold concentrated cerebrospinal fluid (CSF derived from 16 untreated patients with highly active multiple sclerosis (MS we selected a combination of three CSF biomarkers, IL-12p40, CXCL13 and IL-8, for further validation.Concentrations of IL-12p40, CXCL13 and IL-8 were determined in a blinded fashion in CSF samples from an initial cohort (n = 72 and a confirmatory cohort (n = 167 of prospectively collected, untreated subjects presenting for a diagnostic work-up of possible neuroimmunological disorder. Diagnostic conclusion was based on a thorough clinical workup, which included laboratory assessment of the blood and CSF, neuroimaging and longitudinal follow-up. Receiver operating characteristic (ROC curve analysis in conjunction with principal component analysis (PCA, which was used to combine information from all three biomarkers, assessed the diagnostic value of measured biomarkers.Each of the three biomarkers was significantly increased in MS and other inflammatory neurological disease (OIND in comparison to non-inflammatory neurological disorder patients (NIND at least in one cohort. However, considering all three biomarkers together improved accuracy of predicting the presence of intrathecal inflammation to the consistently good to excellent range (area under the ROC curve = 0.868-0.924.Future clinical studies will determine if a combinatorial biomarker consisting of CSF IL-12p40, CXCL13 and IL-8 provides utility in determining the presence of active intrathecal inflammation in diagnostically

  5. Neutralization of IL-8 prevents the induction of dermatologic adverse events associated with the inhibition of epidermal growth factor receptor

    DEFF Research Database (Denmark)

    Bangsgaard, Nannie; Houtkamp, Mischa; Schuurhuis, Danita H;

    2012-01-01

    , characterized by acute follicular neutrophil-rich hair follicle inflammation, and thus mimicked adverse events induced by systemic administration of EGFR inhibitors. In this model, we tested the hypothesis that neutrophils, attracted by IL-8, play a central role in the observed rash. Indeed, concomitant local......Epidermal growth factor receptor (EGFR) inhibitors are widely used in the treatment of cancer. EGFR-targeted treatment is known to be associated with a high incidence of dermatological adverse reactions, including papulopustular rash, which can be dose-limiting and may affect compliance...

  6. Measurement and significance of serum TNF-a, IL-8 and plasma selectin levels in patients with chronic hepatic diseases.%慢性肝病患者血清TNF-α、IL-8和血浆选择素水平的检测及其意义

    Institute of Scientific and Technical Information of China (English)

    罗清逢; 高孝慈; 龙尧; 徐军发; 郑兴武

    2001-01-01

    Objective To investigate the relationship between TNF-a, IL-8, P-selectin and chronic hepatic diseases. Methods The serum TNF-α, IL-8 and plasma selectin levels in 124 patients were measured by ELISA. Results The TNF-α, IL-8 and P-selectin levels are significantly higher than normal controls( P<0.001,P<0.01). Conclusion The measurements of serum TNF-α, IL-8 and P-selectin levels have clinical value for judgement patients condition and prognosis.%目的 探讨TNF-a、IL-8和P-selectin与慢性肝病的关系。方法 应用双抗体夹心酶联免疫吸附法(ELISA)测定124例慢性肝病患者血清TNF-α、IL-8和P-selectin的水平。结果 慢性肝病患者血清TNF-a、IL-8和P-selectin水平均明显高于对照组(P值均<0.001,P-selectin组P<0.01)。结论 TNF-a、IL-8和P-selectin可能参与慢性肝病免疫病理损伤过程。检测血清TNF-α、IL-8和P-selectin水平对判断患者病情和预后有临床实用价值。

  7. Targeting PI3K, HER2 and the IL-8/JAK2 axis in metastatic breast cancer: Which combination makes the whole greater than the sum of its parts?

    Science.gov (United States)

    Britschgi, Adrian; Radimerski, Thomas; Bentires-Alj, Mohamed

    2013-01-01

    The widespread hyperactivation of the PI3K/mTOR pathway in human cancer has made it a prime target for the treatment of this disease. However, a variety of resistance mechanisms involving (re)activation of the targeted pathway or of parallel survival signaling cascades have limited the clinical success of inhibitors targeting PI3K and/or mTOR. Recent studies delineated new crosstalks between PI3K, HER2, JAK2 and IL-8 signaling, which can explain the limited efficacy of PI3K blockade when inhibitors of this pathway are used as single agents. In this review, we summarize molecular mechanisms of resistance to inhibitors of the PI3K/mTOR pathway, provide an outline of new connections between crucial oncogenic signaling pathways, and discuss the potential of new combination therapy approaches to overcome resistance.

  8. Positive Relationship between Total Antioxidant Status and Chemokines Observed in Adults

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    Yanli Li

    2014-01-01

    Full Text Available Objective. Human evidence is limited regarding the interaction between oxidative stress biomarkers and chemokines, especially in a population of adults without overt clinical disease. The current study aims to examine the possible relationships of antioxidant and lipid peroxidation markers with several chemokines in adults. Methods. We assessed cross-sectional associations of total antioxidant status (TAS and two lipid peroxidation markers malondialdehyde (MDA and thiobarbituric acid reactive substances (TBARS with a suite of serum chemokines, including CXCL-1 (GRO-α, CXCL-8 (IL-8, CXCL-10 (IP-10, CCL-2 (MCP-1, CCL-5 (RANTES, CCL-8 (MCP-2, CCL-11 (Eotaxin-1, and CCL-17 (TARC, among 104 Chinese adults without serious preexisting clinical conditions in Beijing before 2008 Olympics. Results. TAS showed significantly positive correlations with MCP-1 (r=0.15751, P=0.0014, MCP-2 (r=0.3721, P=0.0001, Eotaxin-1 (r=0.39598, P<0.0001, and TARC (r=0.27149, P=0.0053. The positive correlations remained unchanged after controlling for age, sex, body mass index, smoking, and alcohol drinking status. No associations were found between any of the chemokines measured in this study and MDA or TBARS. Similar patterns were observed when the analyses were limited to nonsmokers. Conclusion. Total antioxidant status is positively associated with several chemokines in this adult population.

  9. Hepcidin, Cathelicidin-1 and IL-8 as immunological markers of responsiveness in early developmental stages of rainbow trout.

    Science.gov (United States)

    Santana, Paula A; Guzmán, Fanny; Forero, Juan C; Luna, Omar F; Mercado, Luis

    2016-09-01

    During the early developmental stage of salmonids, high mortality occurs largely as a result of pathogens. These cause low immune competence in fry, producing disease, decreasing production and finally leading to economic losses. Therefore, the aim of this study was to characterise the developmental stages in which rainbow trout acquires immune response capability when challenged with LPS from Pseudomona aeruginosa for 8 h, studying the hepcidin, cathelicidin-1 and IL-8. Total RNA was extracted from fry at 34, 42, 56 and 66 days post hatching (dph). Hepcidin and cathelicidin-1 transcripts were detected only at days 34 and 42, whereas the IL-8 transcript was detected from day 34 to day 66. To analyse the protein expression in the fry, polyclonal anti-peptide antibodies were generated in rabbit. These three immune sera demonstrated the ability to recognise the whole molecule in biological samples. Immunofluorescence showed that skin, gills and intestine mainly responded to the LPS challenge, indicating that these portals of pathogen entry are capturing LPS. This study constitutes a valuable approach, since it has the potential to identify molecules with biological activity that can be used to evaluate the status of fry in culture. PMID:27106706

  10. Survival of human epidermal keratinocytes after short-duration high temperature: synthesis of HSP70 and IL-8.

    Science.gov (United States)

    Bowman, P D; Schuschereba, S T; Lawlor, D F; Gilligan, G R; Mata, J R; DeBaere, D R

    1997-06-01

    Thermal injury by short pulses (1-30 s) of relatively high temperature (50-68 degrees C) was investigated in normal human epidermal keratinocytes (NHEK). NHEK were cultured on plastic cover-slips and dipped in medium held at various temperatures. Survival assessed by methylthiazol tetrazolium reduction assay at 6 days postheating demonstrated an inverse time-temperature relationship that indicated that most cells could survive after a 1-s, 60 degrees C exposure or a 30-s, 55 degrees C exposure. Arrhenius plots of the data indicated major transition points for cell injury at 50 and 60 degrees C. Heat shock protein 70 (HSP70) and interleukin-8 (IL-8) were both induced by elevation of temperature between 50 and 60 degrees C for as short a time as 1 s. HSP70 synthesis stimulated by short, high pulses of heat appeared to induce thermotolerance. These results demonstrate that brief exposure to relatively high temperature can induce HSP70 and IL-8 synthesis in keratinocytes. PMID:9227428

  11. Clinical significance of determination of changes of serum TGF-β1, IL-8 and VEGF levels in patients with pregnancy induced hypertension complicated with nephropathy

    International Nuclear Information System (INIS)

    Objective: To explore the significance of changes of serum TGF-β1, IL-8 and VEGF levels in patients with hypertensive disorder complicating pregnancy. Methods: Serum IL-8 (with RIA), serum TGF-β1, VEGF(with ELISA) levels were measured in 33 patients with pregnancy induced hypertension complicated with nephropathy, as well as in 35 healthy controls. Results: The serum TGF-β1, IL-8 and VEGF levels in patients were significantly higher than those in controls (P1 levels were positively correlated to IL-8 (r=0.6132, 0.5834, P<0.01). Conclusion: VEGF levels were closely related with the diseases process of PIH. Determination of their changes might be useful for clinical diagnosis and predicting therapeutic effects in patients with PIH. (authors)

  12. A beginner's guide to chemokines.

    Science.gov (United States)

    Vinader, Victoria; Afarinkia, Kamyar

    2012-05-01

    This review provides an overview of chemokines and their receptors, with an emphasis on general features and nomenclature along with a short summary of their properties and functions. It is intended as an introduction to the subject and a reference point for those wishing to learn key facts about chemokines and their role in biology. PMID:22571610

  13. ERK/Egr-1 signaling pathway is involved in CysLT2 receptor-mediated IL-8 production in HEK293 cells.

    Science.gov (United States)

    Lin, Kana; Fang, Sanhua; Cai, Beilei; Huang, Xueqin; Zhang, Xiayan; Lu, Yunbi; Zhang, Weiping; Wei, Erqing

    2014-07-01

    The CysLT2 receptor is involved in myocardial ischemia/reperfusion injury, differentiation of colorectal cancers, bleomycin-induced pulmonary inflammation and fibrosis. However, the signal transduction of cysteinyl leukotriene receptor 2 (CysLT2) in inflammatory responses remains to be clarified. In HEK293 cells stably expressing hCysLT1, hCysLT2 and rGPR17, we determined the signaling pathways for interleukin-8 (IL-8) production after CysLT2 receptor activation. HEK293 cells were stably transfected with the recombinant plasmids of pcDNA3.1(+)-hCysLT1, pcDNA3.1(+)-hCysLT2 and pcDNA3.1-rGPR17. Leukotriene C4 (LTC4) and LTD4 were used as the agonists to induce IL-8 production and the related changes in signal molecules. We found that LTC4 and LTD4 significantly induced IL-8 promoter activation in the HEK293 cells stably expressing hCysLT2, but not in those expressing hCysLT1 and rGPR17. In hCysLT2-HEK293 cells, LTC4 induced elevation of intracellular calcium, ERK1/2 phosphorylation and Egr-1 expression, and stimulated IL-8 expression and release. These responses were blocked by the selective CysLT2 receptor antagonist HAMI3379. The ERK1/2 inhibitor U0126 inhibited Egr-1 and IL-8 expression as well as IL-8 release, but the JNK and p38 inhibitors did not have the inhibitory effects. Down-regulation of Egr-1 by RNA interference with its siRNA inhibited the LTC4-induced IL-8 expression and release. In conclusion, these findings indicate the ERK-Egr-1 pathway of CysLT2 receptors mediates IL-8 production induced by the pro-inflammatory mediators LTC4 and LTD4.

  14. Association of IL-8-inducing strains of diffusely adherent Escherichia coli with sporadic diarrheal patients with less than 5 years of age

    Directory of Open Access Journals (Sweden)

    Ismail Mustafa Meraz

    2007-02-01

    Full Text Available The role of diffusely adherent Escherichia coli (DAEC in diarrheal disease has been controversial. However, DAEC strains were recently implicated in diarrheal disease in developing countries. To clarify whether DAEC are prevalent among sporadic cases of diarrheal illness in Osaka City, Japan, E. coli strains isolated between July 1997 and March 2000 during diarrheagenic E. coli (DEC investigation were retrospectively examined. DAEC strains were recognized among 41 (4.4% of 924 patients and formed the biggest subgroup of DEC. Previously, we reported that some DAEC strains caused epithelial cells to secrete as much IL-8 as enteroaggregative E. coli strains did. In this study, we attempted to evaluate epidemiologically whether the ability of DAEC to induce IL-8 was involved in the pathogenesis. Relationship among patient age, symptoms, Afa adhesins, season and IL-8 induction were examined. The subgroup of DAEC that possessed Afa genes and/or induced a high level of IL-8 was significantly prevalent among patients age 1 to 4 years; however total DAEC was not significantly high among the children compared to other age group. IL-8 inducing DAEC seems to play a role in causing sporadic diarrheal illnesses, particularly in pediatric fields. Investigations highlighting the relationship between IL-8 induction and enteropathogenicity are clearly necessary to confirm the role of DAEC in infectious enteritis.

  15. 溃疡性结肠炎患者血清IL-6、IL-8、TNF-α水平变化及意义

    Institute of Scientific and Technical Information of China (English)

    任保从

    2010-01-01

    目的 观察溃疡性结肠炎(UC)患者血清IL-6、IL-8、TNF-α水平变化,并探讨其意义.方法 UC患者60例(UC组),对照组30例.采用ELISA法检测两组血清IL-6、IL-8、TNF-α.结果 UC组血清IL-6、IL-8、TNF-α水平明显高于对照组(P均<0.05);重度UC患者血清IL-6、IL-8、TNF-α水平高于轻中度、中度高于轻度 (P均<0.05).结论 UC患者血清IL-6、IL-8、TNF-α水平升高,检测血清IL-6、 IL-8、TNF-α有助于UC病情的判断.

  16. DETERMINATION OF URINE TUMOR NECROSIS FACTOR, IL-6, IL-8 AND SERUM IL-6 IN PATIENTS WITH HEMORRHAGIC FEVERS WITH RENAL SYNDROME

    Institute of Scientific and Technical Information of China (English)

    Fan Wanhu; Chen Ruilin; Yue Jinsheng; Liu Zhengwen; Zhang Shulin

    2006-01-01

    Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome(HFRS). Methods Double-antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine tumor necrosis factor (TNF), IL-6 and IL-8 levels in 56 patients with HFRS. Results Serum IL-6, urine TNF, IL-6 and IL-8 concentrations in HFRS patients were significantly higher than those in control group, respectively (P<0.001). The concentrations increased at fever stage, then continued to increase during hypotension stage and peaked at oliguria stage. The concentrations of serum IL-6, urine TNF, IL-6 and IL-8 increased in accord with the severity of the disease and differed greatly among different types of the disease. Serum IL-6 had remarkable relationships with serum specific antibodies. It was positively related to serum β2-microglobulin (β2-MG), blood ureanitrogen (BUN) and creatinine (Cr). Significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 (r=0.5768, P<0.05; r=0.3760, P<0.01). Conclusion TNF, IL-6 and IL-8 activated during the course of the disease. IL-6 is associated with the immunopathological lesions caused by the hyperfunction of humoral immune response. IL-6, IL-8 and TNF are involved in the renal immune impairment. Determining them might, in certain extent, be used in predicting the prognosis and outcome of patients with HFRS.

  17. Involvement of multiple signaling pathways in the post-bariatric induction of IL-6 and IL-8 mRNA and release in human visceral adipose tissue.

    Science.gov (United States)

    Fain, John N; Bahouth, Suleiman W; Madan, Atul K

    2005-05-01

    The present studies were designed to determine the site of and the mechanism for the rapid increase in IL-6 and IL-8 mRNA observed in human visceral adipose tissue after removal during laparoscopic bariatric surgery. Upregulation of IL-6 and IL-8 mRNA as well as their release were seen within 3h whether one intact piece of tissue or minced pieces of adipose tissue were incubated in vitro. Most of the IL-6 and IL-8 mRNA content of visceral adipose tissue after 3h of incubation was in the non-fat cells. Actinomcyin D markedly reduced the upregulation of IL-6 and IL-8 mRNA. Incubation of adipose tissue explants with a soluble TNFalpha receptor (etanercept) plus a blocking antibody against IL-lbeta reduced by 55% the increase in IL-6 mRNA and by 42% that of IL-8 mRNA seen between 1 and 5h of incubation. The upregulation of IL-8 and IL-6 mRNA accumulation as well as their release over a 2 or 4h incubation was reduced by around 50% in the presence of an inhibitor of the p38 MAPK or an inhibitor of the NFkappaB pathway and by 85% in the presence of both inhibitors. The data suggest that the relative trauma and/or hypoxia that occurs when adipose tissue is removed results in the release of TNFalpha and IL-1beta. These cytokines, and probably other factors as well, enhance IL-6 and IL-8 mRNA accumulation in human adipose tissue explants through mechanisms involving the p38 MAPK and NFkappaB pathways. PMID:15826602

  18. Parthenolide inhibits ERK and AP-1 which are dysregulated and contribute to excessive IL-8 expression and secretion in cystic fibrosis cells

    Directory of Open Access Journals (Sweden)

    Saadane Aicha

    2011-10-01

    Full Text Available Abstract Background Excessive secretion of IL-8 characterizes cystic fibrosis (CF. This has been attributed to excessive activation of epithelial cell I-κB Kinase and/or NFκB. Maximum IL-8 production requires 3 cooperative mechanisms: 1 release of the promoter from repression; 2 activation of transcription by NFκB and AP-1; 3 stabilization of mRNA by p38-MAPK. Little is known about regulation of IL-8 by MAPKs or AP-1 in CF. Methods We studied our hypothesis in vitro using 3-cellular models. Two of these models are transformed cell lines with defective versus normal cystic fibrosis transmembrane conductance regulator (CFTR expression: an antisense/sense transfected cell line and the patient derived IB3-1/S9. In the third series of studies, we studied primary necropsy human tracheal epithelial cells treated with an inhibitor of CFTR function. All cell lines were pretreated with parthenolide and then stimulated with TNFα and/or IL-1β. Results In response to stimulation with TNFα and/or IL-1β, IL-8 production and mRNA expression was greater in CF-type cells than in non-CF controls. This was associated with enhanced phosphorylation of p38, ERK1/2 and JNK and increased activation of AP-1. Since we previously showed that parthenolide inhibits excessive IL-8 production by CF cells, we evaluated its effects on MAPK and AP-1 activation and showed that parthenolide inhibited ERK and AP-1 activation. Using a luciferase promoter assay, our studies showed that parthenolide decreased activation of the IL-8 promoter in CF cells stimulated with TNFα/IL-1β. Conclusions In addition to NFκB MAPKs ERK, JNK and p38 and the transcription factor AP-1 are also dysregulated in CF epithelial cells. Parthenolide inhibited both NFκB and MAPK/AP-1 pathways contributing to the inhibition of IL-8 production.

  19. Interleukin-8 (IL-8) over-production and autocrine cell activation are key factors in monomethylarsonous acid [MMA(III)]-induced malignant transformation of urothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Escudero-Lourdes, C., E-mail: cescuder@uaslp.mx [Centro de Investigación y Estudios de Posgrado (CIEP), Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí (Mexico); Wu, T.; Camarillo, J.M.; Gandolfi, A.J. [Department of Pharmacology and Toxicology College of Pharmacy, University of Arizona. Tucson, AZ (United States)

    2012-01-01

    The association between chronic human exposure to arsenicals and bladder cancer development is well recognized; however, the underlying molecular mechanisms have not been fully determined. We propose that inflammatory responses can play a pathogenic role in arsenic-related bladder carcinogenesis. In previous studies, it was demonstrated that chronic exposure to 50 nM monomethylarsenous acid [MMA(III)] leads to malignant transformation of an immortalized model of urothelial cells (UROtsa), with only 3 mo of exposure necessary to trigger the transformation-related changes. In the three-month window of exposure, the cells over-expressed pro-inflammatory cytokines (IL-1β, IL-6 and IL-8), consistent with the sustained activation of NFKβ and AP1/c-jun, ERK2, and STAT3. IL-8 was over-expressed within hours after exposure to MMA(III), and sustained over-expression was observed during chronic exposure. In this study, we profiled IL-8 expression in UROtsa cells exposed to 50 nM MMA(III) for 1 to 5 mo. IL-8 expression was increased mainly in cells after 3 mo MMA(III) exposure, and its production was also found increased in tumors derived from these cells after heterotransplantation in SCID mice. UROtsa cells do express both receptors, CXCR1 and CXCR2, suggesting that autocrine cell activation could be important in cell transformation. Supporting this observation and consistent with IL-8 over-expression, CXCR1 internalization was significantly increased after three months of exposure to MMA(III). The expression of MMP-9, cyclin D1, bcl-2, and VGEF was significantly increased in cells exposed to MMA(III) for 3 mo, but these mitogen-activated kinases were significantly decreased after IL-8 gene silencing, together with a decrease in cell proliferation rate and in anchorage-independent colony formation. These results suggest a relevant role of IL-8 in MMA(III)-induced UROtsa cell transformation. -- Highlights: ► IL-8 is over-expressed in human MMA(III)-exposed urothelial

  20. 口腔鳞状细胞癌患者唾液中CEA、IL-6、IL-8含量的检测

    Institute of Scientific and Technical Information of China (English)

    杜娟; 颜雨春

    2010-01-01

    目的 通过对口腔鳞状细胞癌(OSCC)患者唾液中癌胚抗原(CEA)、白细胞介素6(IL-6)和白细胞介素8(IL-8)含量的测定和分析,探讨唾液中CEA、IL-6和IL-8含量在口腔鳞状细胞癌诊断中的意义.方法 选取35例OSCCT1或T2期患者为病例组,35例身体健康的正常人为对照组.采用ELISA法测定所有样本唾液中的CEA、IL-6和IL-8含量.结果 OSCC患者唾液中的CEA、IL-6和IL-8浓度均显著高于正常人,差异具有统计学意义(P<0.01).结论 唾液中CEA、IL-6和IL-8的含量对诊断OSCC具有一定的临床意义,唾液中肿瘤标记物的检测可作为诊断OSCC的一种辅助手段.

  1. The Effect of Therapeutic Blockades of Dust Particles-Induced Ca2+ Signaling and Proinflammatory Cytokine IL-8 in Human Bronchial Epithelial Cells

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    Ju Hee Yoon

    2015-01-01

    Full Text Available Bronchial epithelial cells are the first barrier of defense against respiratory pathogens. Dust particles as extracellular stimuli are associated with inflammatory reactions after inhalation. It has been reported that dust particles induce intracellular Ca2+ signal, which subsequently increases cytokines production such as interleukin- (IL- 8. However, the study of therapeutic blockades of Ca2+ signaling induced by dust particles in human bronchial epithelial cells is poorly understood. We investigated how to modulate dust particles-induced Ca2+ signaling and proinflammatory cytokine IL-8 expression. Bronchial epithelial BEAS-2B cells were exposed to PM10 dust particles and subsequent mediated intracellular Ca2+ signaling and reactive oxygen species signal. Our results show that exposure to several inhibitors of Ca2+ pathway attenuated the PM10-induced Ca2+ response and subsequent IL-8 mRNA expression. PM10-mediated Ca2+ signal and IL-8 expression were attenuated by several pharmacological blockades such as antioxidants, IP3-PLC blockers, and TRPM2 inhibitors. Our results show that blockades of PLC or TRPM2 reduced both of PM10-mediated Ca2+ signal and IL-8 expression, suggesting that treatment with these blockades should be considered for potential therapeutic trials in pulmonary epithelium for inflammation caused by environmental events such as seasonal dust storm.

  2. Zerumbone suppresses IL-1β-induced cell migration and invasion by inhibiting IL-8 and MMP-3 expression in human triple-negative breast cancer cells.

    Science.gov (United States)

    Han, Jeonghun; Bae, Soo Youn; Oh, Soo-Jin; Lee, Jeongmin; Lee, Jun Ho; Lee, Hyun-Chul; Lee, Se Kyung; Kil, Won Ho; Kim, Seok Won; Nam, Seok Jin; Kim, Sangmin; Lee, Jeong Eon

    2014-11-01

    Inflammation is a key regulatory process in cancer development. Prolonged exposure of breast tumor cells to inflammatory cytokines leads to epithelial-mesenchymal transition, which is the principal mechanism involved in metastasis and tumor invasion. Interleukin (IL)-1β is a major inflammatory cytokine in a variety of tumors. To date, the regulatory mechanism of IL-1β-induced cell migration and invasion has not been fully elucidated. Here, we investigated the effect of zerumbone (ZER) on IL-1β-induced cell migration and invasion in breast cancer cells. The levels of IL-8 and matrix metalloproteinase (MMP)-3 mRNA were analyzed by real-time polymerase chain reaction. The levels of secreted IL-8 and MMP-3 protein were analyzed by enzyme-linked immunosorbent assay and western blot analysis, respectively. Cell invasion and migration was detected by Boyden chamber assay. The levels of IL-8 and MMP-3 expression were significantly increased by IL-1β treatment in Hs578T and MDA-MB231 cells. On the other hand, IL-1β-induced IL-8 and MMP-3 expression was decreased by ZER. Finally, IL-1β-induced cell migration and invasion were decreased by ZER in Hs578T and MDA-MB231 cells. ZER suppresses IL-1β-induced cell migration and invasion by inhibiting IL-8 expression and MMP-3 expression in TNBC cells. ZER could be a promising therapeutic drug for treatment of triple-negative breast cancer patients.

  3. Triptolide suppresses IL-1β-induced chemokine and stromelysin-1 gene expression in human colonic subepithelial myofibroblasts

    Institute of Scientific and Technical Information of China (English)

    Qing-song TAO; Jian-an REN; Jie-shou LI

    2007-01-01

    Aim: To examine the inhibitive effects of triptolide on the expression of IL-8, monocyte chemotactic protein (MCP)-1, and matrix metalloproteinases (MMP)-3 in subepithelial myofibroblasts (SEMF) stimulated with IL-1β. Methods: SEMF cultures were established from normal colons in patients who underwent gut resection for colorectal carcinoma. Chemokine and MMP-3 expressions were determined by ELISA and RT-PCR. The cytosolic amount of phosphorylation of IκB-α (p-IκB-α) was determined by Western blotting. The DNA binding capacity of NF-κB was evaluated by electrophoretic mobility shift assays. Results: IL-1βstimulated protein and mRNA expression of IL-8, MCP-1, and MMP-3 in SEMF,Triptolide inhibited these effects of IL-1β in a dose-dependent manner. Mecha-nistic studies revealed that triptolide markedly decreased IL-1β-induced NF- κB DNA binding capacity and cytosolic amount of p-IκB-α. These results showed that triptolide inhibited IL-1β-induced chemokine and MMP-3 expression in SEMF through the NF-κB pathway. Conclusion: Triptolide inhibited IL-1β-induced chemokine and MMP-3 expression in SEMF by preventing the phosphorylation of IκB-α.

  4. Polarized secretion of interleukin (IL-6 and IL-8 by human airway epithelia 16HBE14o- cells in response to cationic polypeptide challenge.

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    Alison Wai-ming Chow

    Full Text Available BACKGROUND: The airway epithelium participates in asthmatic inflammation in many ways. Target cells of the epithelium can respond to a variety of inflammatory mediators and cytokines. Damage to the surface epithelium occurs following the secretion of eosinophil-derived, highly toxic cationic proteins. Moreover, the surface epithelium itself is responsible for the synthesis and release of cytokines that cause the selective recruitment, retention, and accumulation of various inflammatory cells. To mimic the damage seen during asthmatic inflammation, the bronchial epithelium can be challenged with highly charged cationic polypeptides such as poly-L-arginine. METHODOLOGY/PRINCIPAL FINDINGS: In this study, human bronchial epithelial cells, 16HBE14o- cells, were "chemically injured" by exposing them to poly-l-arginine as a surrogate of the eosinophil cationic protein. Cytokine antibody array data showed that seven inflammatory mediators were elevated out of the 40 tested, including marked elevation in interleukin (IL-6 and IL-8 secretion. IL-6 and IL-8 mRNA expression levels were elevated as measured with real-time PCR. Cell culture supernatants from apical and basolateral compartments were collected, and the IL-6 and IL-8 production was quantified with ELISA. IL-6 and IL-8 secretion by 16HBE14o- epithelia into the apical compartment was significantly higher than that from the basolateral compartment. Using specific inhibitors, the production of IL-6 and IL-8 was found to be dependent on p38 MAPK, ERK1/2 MAPK, and NF-kappaB pathways. CONCLUSIONS/SIGNIFICANCE: The results clearly demonstrate that damage to the bronchial epithelia by poly-L-arginine stimulates polarized IL-6 and IL-8 secretion. This apically directed secretion of cytokines may play an important role in orchestrating epithelial cell responses to inflammation.

  5. RETRACTED: Blockade of TNF-α signaling suppresses the AREG-mediated IL-6 and IL-8 cytokines secretion induced by anti-Ro/SSA autoantibodies.

    Science.gov (United States)

    Sisto, Margherita; Lisi, Sabrina; Lofrumento, Dario Domenico; Cucci, Liana; Mitolo, Vincenzo; D'Amore, Massimo

    2010-09-20

    The aim of this study was to analyze the Furin-TNF-α-converting enzyme (TACE)-amphiregulin (AREG)-IL-6/IL-8 secretion pathway in non-neoplastic human salivary gland epithelial cells (SGECs) stimulated with anti-Ro/SSA autoantibodies (Abs). We examined whether anti-Ro/SSA Abs-mediated TACE activation is responsible for AREG activation. As recent studies have demonstrated that AREG could induce proinflammatory cytokines secretion in epithelial cells, we discuss how TACE-mediated AREG shedding, caused by anti-Ro/SSA Abs treatment, could have a critical role in TNF-α-induced IL-6 and IL-8 secretion by SGEC. Furthermore, the effects of TNF-α blockade on AREG expression and TNF-α-AREG-mediated IL-6 and IL-8 secretion were evaluated. We have discovered that the upregulation of AREG occurs through TNF-α produced after anti-Ro/SSA Abs uptake via Fcγ receptors. Biological drug adalimumab and the gene silencing technique were used to study the AREG-IL-6/IL-8 secretion pathway, demonstrating that (i) adalimumab-mediated TNF-α blocking and TNF-α gene silencing provoke a significant decrease of proinflammatory cytokines production and AREG expression in anti-Ro/SSA Abs-treated SGEC; (ii) AREG gene silencing has a potent inhibitory effect on TNF-α-induced IL-6 and IL-8 secretion in SGEC treated with anti-Ro/SSA Abs; (iii) an inspection of the kinetics of cytokine production after exogeni TNF-α and AREG addition, and the use of cycloheximide in the presence of exogenous TNF-α as stimulant, clarified that TNF-α induces IL-6 and IL-8 secretion through AREG.Laboratory Investigation advance online publication, 20 September 2010; doi:10.1038/labinvest.2010.168.

  6. Determination of urine tumor necrosis factor, IL-6, IL-8, and serum IL-6 in patients with hemorrhagic fever with renal syndrome

    Directory of Open Access Journals (Sweden)

    Wanhu Fan

    2012-12-01

    Full Text Available OBJECTIVE: The aim of this study was to explore the role of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome (HFRS. METHODS: Double-antibody sandwich ELISA was used to determine serum interleukin (IL-6, urine tumor necrosis factor (TNF, IL-6, and IL-8 levels in 56 patients with HFRS. RESULTS: Serum IL-6, urine TNF, IL-6, and IL-8 concentrations in HFRS patients were significantly higher than those in the control group (p < 0.001. the concentrations increased at fever stage, then continued to increase during the hypotension stage and peaked at the oliguria stage. the concentrations of serum IL-6, urine TNF, IL-6, and IL-8 increased according to the severity of the disease, and differed greatly among different types of the disease. serum IL-6 had remarkable relationships with serum specific antibodies. it was positively related to serum 12-microglobulin (β-mg, blood ureanitrogen (bun, and creatinine (Cr. significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 (r = 0.5768, p < 0.05; r = 0.3760, p < 0.01. CONCLUSION: TNF, IL-6, and IL-8 were activated during the course of the disease. IL-6 was associated with the immunopathological lesions caused by the hyperfunction of the humoral immune response. IL-6, IL-8 and TNF were involved in renal immune impairment. determining them might, to a certain extent, be useful in predicting the prognosis and outcome of patients with hfrs.

  7. Closing escape routes: inhibition of IL-8 signaling enhances the anti-tumor efficacy of PI3K inhibitors.

    Science.gov (United States)

    Juvekar, Ashish; Wulf, Gerburg M

    2013-04-08

    The phosphoinositide 3-kinase (PI3K) pathway serves as a relay where signals that emanate from the cell membrane are received and converted into intracellular signals that promote proliferation and survival. Inhibitors of PI3K hold promise for the treatment of breast cancer because activation of this pathway is highly prevalent. However, as is increasingly observed with inhibitors of cell signaling, there appear to be mechanisms of primary and secondary resistance. Britschgi and colleagues report that compensatory activation of the IL-8 signaling axis is a mechanism of primary resistance to PI3K inhibitors in some triple-negative breast cancers. In a set of experiments that carefully emulate the clinical scenario in a mouse model, they show that simultaneous inhibition of Janus kinase 2 enhances the efficacy of PI3K/mammalian target of rapamycin inhibition. Their paper lends further support to the concept that successful design of treatments with signal transduction inhibitors must anticipate potential escape routes - and include agents to simultaneously block them.

  8. Cytokine modulation (IL-6, IL-8, IL-10) by human breast milk lipids on intestinal epithelial cells (Caco-2).

    Science.gov (United States)

    Barrera, Girolamo J; Sánchez, Gabriela

    2016-08-01

    Human breast milk is the best form of nourishment for infants during the first year of life. It is composed by a complex mixture of carbohydrates, proteins and fats. Breast milk provides nutrients and bioactive factors that themselves modulate maturation and development of the gastrointestinal tract. Many studies have shown that it provides protection against gastrointestinal tract inflammation. In this sense, this study aimed to evaluate the effect of human breast milk lipids on epithelial intestinal cells (Caco-2) cytokine regulation and the fatty acid transporter protein (FATP) involved in this process. Caco-2 cells were cultivated and stimulated with different concentration of human milk lipids from healthy human mothers (18-30-year-olds) or single commercial lipids for 48 h. We measured the concentrations and mRNA levels of IL-6, IL-8 and IL-10 cytokines by immunoassay (ELISA) and quantitative-PCR (qRT-PCR) technique, respectively. We observed a two to three times decrease in pro-inflammatory cytokine levels (p < 0.01) as well as an increase in anti-inflammatory IL-10 levels in cells stimulated with increasing concentrations of breast milk lipids. These results suggest that human breast milk lipids could have an important role on the cytokine modulation in the newborn bowel. PMID:26441050

  9. Streptococcus pneumoniae induced c-Jun-N-terminal kinase- and AP-1 -dependent IL-8 release by lung epithelial BEAS-2B cells

    Directory of Open Access Journals (Sweden)

    Rosseau Simone

    2006-07-01

    Full Text Available Abstract Background Although pneumococcal pneumonia is one of the most common causes of death due to infectious diseases, little is known about pneumococci-lung cell interaction. Herein we tested the hypothesis that pneumococci activated pulmonary epithelial cell cytokine release by c-Jun-NH2-terminal kinase (JNK Methods Human bronchial epithelial cells (BEAS-2B or epithelial HEK293 cells were infected with S. pneumoniae R6x and cytokine induction was measured by RT-PCR, ELISA and Bioplex assay. JNK-phosphorylation was detected by Western blot and nuclear signaling was assessed by electrophoretic mobility shift assay (EMSA and chromatin immunoprecipitation (ChIP. JNK was modulated by the small molecule inhibitor SP600125 and AP1 by transfection of a dominant negative mutant. Results S. pneumoniae induced the release of distinct CC and CXC, as well as Th1 and Th2 cytokines and growth factors by human lung epithelial cell line BEAS-2B. Furthermore, pneumococci infection resulted in JNK phosphorylation in BEAS-2B cells. Inhibition of JNK by small molecule inhibitor SP600125 reduced pneumococci-induced IL-8 mRNA expression and release of IL-8 and IL-6. One regulator of the il8 promoter is JNK-phosphorylated activator protein 1 (AP-1. We showed that S. pneumoniae time-dependently induced DNA binding of AP-1 and its phosphorylated subunit c-Jun with a maximum at 3 to 5 h after infection. Recruitment of Ser63/73-phosphorylated c-Jun and RNA polymerase II to the endogenous il8 promoter was found 2 h after S. pneumoniae infection by chromatin immunoprecipitation. AP-1 repressor A-Fos reduced IL-8 release by TLR2-overexpressing HEK293 cells induced by pneumococci but not by TNFα. Antisense-constructs targeting the AP-1 subunits Fra1 and Fra2 had no inhibitory effect on pneumococci-induced IL-8 release. Conclusion S. pneumoniae-induced IL-8 expression by human epithelial BEAS-2B cells depended on activation of JNK and recruitment of phosphorylated c

  10. Presence of terminal EPIYA phosphorylation motifs in Helicobacter pylori CagA contributes to IL-8 secretion, irrespective of the number of repeats.

    Directory of Open Access Journals (Sweden)

    Konstantinos S Papadakos

    Full Text Available CagA protein contributes to pro-inflammatory responses during H. pylori infection, following its intracellular delivery to gastric epithelial cells. Here, we report for the first time in an isogenic background, on the subtle role of CagA phosphorylation on terminal EPIYA-C motifs in the transcriptional activation and expression of IL-8. We utilized isogenic H. pylori mutants of P12 reference strain, expressing CagA with varying number of EPIYA-C motifs and the corresponding phosphorylation defective EPIFA-C motifs while preserving intact the CM multimerization motifs. These mutants had been previously closely scrutinized in terms of type IV secretion system functionality, CagA translocation and its subsequent phosphorylation. Following infection of gastric epithelial cell lines, transcriptional activation of IL-8 gene and secreted IL-8 levels were found to be strictly dependent upon the functionality of the EPIYA-C phosphorylation motifs, as EPIFA-C phosphorylation-deficient CagA expression failed to induce full IL-8 transcriptional activity. Interestingly, levels of IL-8 gene activation and of secreted IL-8 were the same, irrespective of the number of EPIYA-C terminal repeats. We monitored IkBα phosphorylation and confirmed CagA involvement in NF-kB activation. Furthermore, we observed that presence of EPIYA-C functional phosphorylation motifs contributed to NF-kB activation. NF-kB upstream signaling events, such as early ERK1/2 and AKT activation were confirmed to be independent of EPIYA-C phosphorylation. On the contrary, use of TAK1 specific inhibitor 5Z-7-Oxozeaenol resulted in complete arrest of IL-8 secretion, in a dose-dependent manner, irrespective of CagA status. H. pylori-infected TAK1(-/- mouse embryonic fibroblasts (MEFs failed to induce NF-kB activity, unlike the respective control MEFs. CagA and TAK1 were found to immunoprecipitate together, irrespective of CagA EPIYA-C status, thus confirming earlier reports of TAK1 and Cag

  11. Inhibition effect of luteolin on IL-8 signal path in breast cancer cells MDA MB 231%Luteolin抑制乳腺癌细胞MDA-MB231增殖及IL-8信号通路的实验研究

    Institute of Scientific and Technical Information of China (English)

    李文仿; 周科; 赵宗彬; 王明华; 王耕

    2014-01-01

    目的:探讨木犀草素(Luteolin)对乳腺癌细胞MDA-MB231增殖及IL-8信号通路的抑制作用.方法:采用不同浓度的Luteolin处理乳腺癌细胞MDA-MB231,观察MDA-MB231细胞的增殖、IL-8蛋白和mRNA的表达以及AKT、ERK的表达.结果:Luteolin可抑制MDA-MB231细胞的增殖和IL-8的分泌,并明显抑制IL-8对乳腺癌细胞的激活.结论:Luteolin是重要的乳腺癌抑制剂,在预防乳腺癌复发及转移中可能有重要的作用.

  12. 支气管肺炎患儿治疗前后血清IGF-Ⅱ、IL-6、IL-8和TNF-α检测的临床意义%Clinical Significance of Determination of Changes of Serum IGF-Ⅱ,IL-6,IL-8,TNF-α Levels After Treatment in Children with Bronchopneamonia

    Institute of Scientific and Technical Information of China (English)

    冯越

    2011-01-01

    Objective To explore the clinical significance of changes of serum IGF-Ⅱ; IL-6; IL-8 and TNF-α levels after treatment in children with bronchopneamonia. Methods Serum IGF- Ⅱ; IL-6; IL-8 and TNF-a levels with RIA were detected both before and after treatment in 33 patients with children bronchopneumonia as well as in 35 controls. Results Before treatment; serum IGF-Ⅱ; IL-6; IL-8 and TNF-a levels were significantly higher in the patients than those in the controls ( P 0. 05 ) . Conclusions Seram IGF- Ⅱ; IL-6; IL-8 and TNF-a could take part in the pathogenesis of children bronchopneumonia in various ways and determination of these levels was clinically important.%目的:探讨支气管肺炎患儿治疗前后血清IGF-Ⅱ、IL-6、IL-8和TNF-α的变化及其临床意义.方法:应用放射免疫分析对33例支气管肺炎患儿进行了治疗前后血清IGF-Ⅱ、IL-6 、IL-8和TNF-α检测,并与35名正常健康儿作比较.结果:支气管肺炎患儿在治疗前血清IGF-Ⅱ、IL-6、IL-8和TNF-α水平显著地高于正常儿组(P<0.01).结论:IGF-Ⅱ、IL-6、IL-8和TNF-α以不同的方式参与了患儿的发病,其水平的检测对了解病情、指导治疗具有重要的临床价值.

  13. 清肺口服液对呼吸道合胞病毒肺炎患儿血清IL-8、ICAM-1表达水平的影响%Influence of Qingfei Oral Liquid on Expressions of Serum IL-8 and ICAM-1 in Children with Respiratory Syncytial Viral Pneumonia

    Institute of Scientific and Technical Information of China (English)

    袁斌; 王爱华; 徐建亚; 朱越; 李琳

    2013-01-01

    Objective:To study the influence of Qingfei Oral Liquid on serum levels of Interleukin -8 (IL-8) and Intercellular adhesion molecule - 1 ( ICAM - 1) in children with respiratory syncytial viral pneumonia. Methods: Enzyme - linked immuno -sorbent assay was used to measure the levels of serum IL-8 and ICAM - 1 in 8 children with respiratory syncytial viral pneumonia before and after the treatment with Qingfei Oral Liquid. Results:The level of serum IL-8 was obviously decreased, while the level of serum ICAM - 1 was obviously increased compared with those before treatment with Qingfei Oral Liquid, and the difference had a statistical significance (P <0. 05). Conclusion: Qingfei Oral Liquid can make the level of serum IL-8 lower and that of ICAM - 1 higher in 8 children with respiratory syncytial viral pneumonia.%目的:探讨清肺口服液对呼吸道合胞病毒肺炎患儿血清白介素-8(IL-8)、细胞间黏附分子-1(ICAM-1)的影响.方法:采用酶联免疫吸附法(ELISA),测量8例RSV肺炎患儿治疗前后血清中IL-8、ICAM-1水平.结果:清肺口服液治疗后患儿血清中IL-8水平比治疗前显著下降,而血清中ICAM-1水平比治疗前显著升高,差异有统计学意义(P<0.05).结论:清肺口服液可显著降低RSV肺炎患儿血清中IL-8水平,升高ICAM-1水平,可能与清肺口服液的免疫调节作用有关.

  14. Changes and clinical significances of sP-selectin and IL-8 in patients with colorectal carcinoma%结直肠癌患者血清sP-selectin和IL-8 水平的变化及其临床意义

    Institute of Scientific and Technical Information of China (English)

    孟明; 陈冬志

    2003-01-01

    目的探讨结直肠癌患者手术前后血清中可溶性P-selectin和IL-8含量的变化及其临床意义.方法用ELISA法和RIA法分别测定结直肠癌患者手术前,手术后及复发病人血清sP-selectin和IL-8的含量,并与对照组进行比较.结果结直肠癌患者血清sP-selectin和IL-8的含量明显高于正常人(P<0.01),术后3个月下降至接近正常人水平,而复发患者则再次升高(P<0.01).结论血清sP-selectin和IL-8的含量与结直肠癌的发生,发展及预后密切相关.%Objective: To investigate the changes and clinical significance of sP- selectin and IL- 8 in patients with colorectal carcinoma before and after operation. Methods: ELISA and RIA methods were used to examine the levels of sP - selectin and IL- 8 respectively before operation, after operation and after relapse. Results:The levels of sP- selectin and IL- 8 in patients with colorectal carcinoma were significantly higher than tbose in control group ( P <0.01), decreased and approached to those in control group 3 months after operation, and increased again when colorectal carcinoma relapsed (P < 0.01 ). Conclusions: The levels of sP - selectin and IL - 8 in patients with colorectal carcinoma were relative to the development and relapse of colorectal carcinoma.

  15. Influence of functional polymorphisms in TNF-α, IL-8, and IL-10 cytokine genes on mRNA expression levels and risk of gastric cancer.

    Science.gov (United States)

    de Oliveira, Juliana Garcia; Rossi, Ana Flávia Teixeira; Nizato, Daniela Manchini; Cadamuro, Aline Cristina Targa; Jorge, Yvana Cristina; Valsechi, Marina Curado; Venâncio, Larissa Paola Rodrigues; Rahal, Paula; Pavarino, Érika Cristina; Goloni-Bertollo, Eny Maria; Silva, Ana Elizabete

    2015-12-01

    Functional polymorphisms in promoter regions can produce changes in the affinity of transcription factors, thus altering the messenger ribonucleic acid (mRNA) expression levels of inflammatory cytokines associated with the risk of cancer development. The goal of this study was to evaluate the influence that polymorphisms in the cytokine genes known as TNF-α-308 G/A (rs1800629), TNF-α-857 C/T (rs1799724), IL-8-251 T/A (rs4073), IL-8-845 T/C (rs2227532), and IL-10-592 C/A (rs1800872) have on changes to mRNA expression levels and on the risks of chronic gastritis (CG) and gastric cancer (GC). A sample of 723 individuals was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Relative mRNA expression levels were measured using quantitative real-time PCR (qPCR). Polymorphisms TNF-α-308 G/A and IL-8-251 A/T were not associated with risks of these gastric lesions. However, TNF-α-857 C/T, IL-8-845 T/C, and IL-10-592 C/A were found to be associated with a higher risk of GC, and IL-10-592 C/A was found to be associated with a higher risk of CG. The relative mRNA expression levels (RQ) of TNF-α, IL-8, and IL-10 were markedly downregulated in the CG group (median RQs = 0.128, 0.247, and 0.614, respectively), while the RQ levels of TNF-α in the GC group were upregulated (RQ = 2.749), but were basal for IL-8 (RQ = 1.053) and downregulated for IL-10 (RQ = 0.179). When the groups were stratified according to wild-type and polymorphic alleles, only for IL-8-845 T/C the polymorphic allele was found to influence the expression levels of this cytokine. IL-8-845 C allele carriers were significantly upregulated in both groups (GC and CG; RQ = 3.138 and 2.181, respectively) when compared to TT homozygotes (RQ = -0.407 and 0.165, respectively). In silico analysis in the IL-8 promoter region revealed that the presence of the variant C allele in position -845 is responsible for the presence of the binding

  16. The Maternal Cytokine and Chemokine Profile of Naturally Conceived Gestations Is Mainly Preserved during In Vitro Fertilization and Egg Donation Pregnancies.

    Science.gov (United States)

    Martínez-Varea, Alicia; Pellicer, Begoña; Serra, Vicente; Hervás-Marín, David; Martínez-Romero, Alicia; Bellver, José; Perales-Marín, Alfredo; Pellicer, Antonio

    2015-01-01

    This prospective longitudinal study aimed at comparing maternal immune response among naturally conceived (NC; n = 25), in vitro fertilization (IVF; n = 25), and egg donation (ED; n = 25) pregnancies. The main outcome measures were, firstly, to follow up plasma levels of interleukin (IL) 1 beta, IL2, IL4, IL5, IL6, IL8, IL10, IL17, interferon gamma, tumor necrosis factor-alpha (TNFα), transforming growth factor-beta (TGFβ), regulated upon activation normal T-cell expressed and secreted (RANTES), stromal cell-derived factor 1 alpha (SDF1α), and decidual granulocyte-macrophage colony-stimulating factor (GM-CSF) during the three trimesters of pregnancy during the three trimesters of pregnancy; secondly, to evaluate if the cytokine and chemokine pattern of ED pregnant women differs from that of those with autologous oocytes and, thirdly, to assess if women with preeclampsia show different cytokine and chemokine profile throughout pregnancy versus women with uneventful pregnancies. Pregnant women in the three study groups displayed similar cytokine and chemokine pattern throughout pregnancy. The levels of all quantified cytokines and chemokines, except RANTES, TNFα, IL8, TGFβ, and SDF1α, rose in the second trimester compared with the first, and these higher values remained in the third trimester. ED pregnancies showed lower SDF1α levels in the third trimester compared with NC and IVF pregnancies. Patients who developed preeclampsia displayed higher SDF1α plasma levels in the third trimester. PMID:26346343

  17. The Maternal Cytokine and Chemokine Profile of Naturally Conceived Gestations Is Mainly Preserved during In Vitro Fertilization and Egg Donation Pregnancies

    Directory of Open Access Journals (Sweden)

    Alicia Martínez-Varea

    2015-01-01

    Full Text Available This prospective longitudinal study aimed at comparing maternal immune response among naturally conceived (NC; n=25, in vitro fertilization (IVF; n=25, and egg donation (ED; n=25 pregnancies. The main outcome measures were, firstly, to follow up plasma levels of interleukin (IL 1beta, IL2, IL4, IL5, IL6, IL8, IL10, IL17, interferon gamma, tumor necrosis factor-alpha (TNFα, transforming growth factor-beta (TGFβ, regulated upon activation normal T-cell expressed and secreted (RANTES, stromal cell-derived factor 1 alpha (SDF1α, and decidual granulocyte-macrophage colony-stimulating factor (GM-CSF during the three trimesters of pregnancy during the three trimesters of pregnancy; secondly, to evaluate if the cytokine and chemokine pattern of ED pregnant women differs from that of those with autologous oocytes and, thirdly, to assess if women with preeclampsia show different cytokine and chemokine profile throughout pregnancy versus women with uneventful pregnancies. Pregnant women in the three study groups displayed similar cytokine and chemokine pattern throughout pregnancy. The levels of all quantified cytokines and chemokines, except RANTES, TNFα, IL8, TGFβ, and SDF1α, rose in the second trimester compared with the first, and these higher values remained in the third trimester. ED pregnancies showed lower SDF1α levels in the third trimester compared with NC and IVF pregnancies. Patients who developed preeclampsia displayed higher SDF1α plasma levels in the third trimester.

  18. Association of H pylori cagA and vacA genotypes and IL-8 gene polymorphisms with clinical outcome of infection in Iranian patients with gastrointestinal diseases

    Institute of Scientific and Technical Information of China (English)

    Eskandar Kamali-Sarvestani; Abdulah Bazargani; Malihe Masoudian; Kamran Lankarani; Ali-Reza Taghavi; Mehdi Saberifiroozi

    2006-01-01

    AIM: To find out if a functional promoter polymorphism in the IL-8 gene along with cagA status and polymorphisms in vac4 gene influence the type of diseases in Iranian patients infected by H pylori.METHODS: IL-8 -251 A/T polymorphism was genotypedby oligonucleotide allele specific PCR (ASO-PCR) in a sample of 233 patients with H pylori infection undergoing upper gastrointestinal endoscopy. The presence of cagA gene and polymorphisms in vacA gene was also determined by PCR. Association of these genetic polymorphisms with the development of gastritis, peptic ulcers as well as gastric cancer was tested. RESULTS: When the patients with different clinical manifestations were compared according to the presence of cagA gene or various vacA genotypes, only the vacA genotypes were significantly different among gastritis, peptic ulcer and gastric cancer patients (x2= 17.8; P =0.001). Furthermore, there was a significant difference in the frequency of IL-8 -251 A/T genotypes between patients with gastric cancer and benign diseases (x2=10.47; P = 0.005).CONCLUSION: The IL-8 -251 A/T polymorphism and the polymorphisms in H pylori vacA gene are involved in limiting the infection outcome to gastritis and peptic ulcer or in favoring cancer onset in Iranian patients.

  19. Chromosomal assignment of six genes (EIF4G3, HSP90, RBBP6, IL8, TERT, and TERC) in four species of the genus Equus.

    Science.gov (United States)

    Vidale, Pamela; Piras, Francesca M; Nergadze, Solomon G; Bertoni, Livia; Verini-Supplizi, Andrea; Adelson, David; Guérin, Gérard; Giulotto, Elena

    2011-01-01

    We mapped six genes (EIF4G3, HSP90, RBBP6, IL8, TERT, and TERC) on the chromosomes of Equus caballus, Equus asinus, Equus grevyi, and Equus burchelli by fluorescence in situ hybridization. Our results add six type I markers to the cytogenetic map of these species and provide new information on the comparative genomics of the genus Equus.

  20. The diagnostic value of CRP, IL-8, PCT, and sTREM-1 in the detection of bacterial infections in pediatric oncology patients with febrile neutropenia

    NARCIS (Netherlands)

    Miedema, Karin G. E.; de Bont, Eveline S. J. M.; Elferink, Rob F. M. Oude; van Vliet, Michel J.; Nijhuis, Claudi S. M. Oude; Kamps, Willem A.; Tissing, Wim J. E.

    2011-01-01

    In this study, we evaluated C-reactive protein (CRP), interleukin (IL)-8, procalcitonin (PCT), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as predictors for bacterial infection in febrile neutropenia, plus their usefulness in febrile neutropenia during chemotherapy-induced

  1. 肩周炎患者推拿治疗前后血清IL-8,IL-32,IL-18检测的临床意义%Clinical Significance of Weasuremeat of Changes of Serum IL-8,IL-32,IL-18 Levels after massage therapy in Patients With periarthritis of Shoulder Diseases

    Institute of Scientific and Technical Information of China (English)

    孙黎明

    2013-01-01

    Objective: To explore the Clinical Significance of Changes of Serum IL-8,IL-32,IL-18 levels after massage therapy in patients with periarthrits of Shoulder Diseases. Methods: Serum IL-8(with RIA) Serum IL-32,IL-18(with EL:SA) levels were determined both before and after massage therapy in 31patients with periarthritis of shoulder diseases as wel as in 35 controls. Results: Before massage therapy the Serum IL-8,IL-32 and IL-18 levels in the patients were significantly higher than those in controls(P0.05), Serum IL-8 levels were positive correlated with Serum IL-32,IL-18 levels(r=0.6118,0.4982, P<0.01). Conclusions: Detection of Serum IL-8,IL-32 and IL-18 levels were closely related to the occurrence and development of the diseases also provides important value clinical y.%目的探讨了肩周炎患者治疗前后血清IL-8,IL-32和IL-18水平的变化及意义。方法应用放射免疫分析法和酶联法对31例肩周炎患者进行了推拿治疗前后血清IL-8,IL-32和IL-18水平检测,并与35名正常健康人作比较。结果肩周炎患者在推拿治疗前血清IL-8,IL-32和IL-18水平均非常显著地高于正常人(P<0.01),经推拿治疗2周后则与正常人比较无显著性差异(P>0.05),且血清IL-8水平与IL-32,IL-18水平呈显著正相关(r=0.6118,0.4982, P<0.01)。结论检测血清IL-8,IL-32和IL-18水平的变化与疾病的发生发展密切相关,具有重要的临床价值。

  2. COPD患者血清IL-6、IL-8、hs-CRP和IL-18检测的临床意义%Clinical Relevance of Determination the Changes on Serum IL-6, IL-8,hs-CRP and IL-18 Levels in Patients with Chronic Obstructive Pulmonary Diseases(COPD)

    Institute of Scientific and Technical Information of China (English)

    赵庆琪; 姚加平

    2012-01-01

    目的:观察慢性阻塞性肺疾病(COPD)患者治疗前后血清IL-6、IL-8、hs-CRP和IL-18水平的变化及临床意义.方法:应用放射免疫分析和免疫比浊法对32例COPD患者进行了治疗前后血清IL-6、IL-8、hs-CRP和IL-8检测,并与35名正常健康人作比较.结果:COPD患者在治疗前血清IL-6、IL-8、hs-CRP和IL-18水平均非常显著地高于正常人组(P<0.01),经中西医结合治疗1个月后与正常人组比较仍有差异(P<0.05).结论:IL-6、IL-8、hs-CRP和IL-18的测定,可适用为一种筛选方法,其变化可能以不同的方式参与了COPD的发病,此外,该些项目的检测对了解病情、指导治疗具有重要的临床价值.%Objective To observe the clinical significance of changes on serum IL-6, IL-8, hs-CRP and BL-18 levels after treatment in patients with COPD. Methods Serum 11-6, IL-8 (with RIA) , serum hs-CRP(with immunotubidimetry) levels were measured both before and after treatment in 32 patients with COPD as well as in 35 normal controls. Results Before treatment, the serum IL-6, IL-8, hs-CRP, IL-18 levels were significantly higher than those in controls (P < 0.01). After 1 month of treatment the serum IL-6, IL-8, hs-CRP and IL-18 dropped markedly but remained higher difference than those in controls ( P < 0.05 ). Conclusion Measurement of serum IL-6,IL-8,hs-CRP and IL-18 were suitable to be used as a screening method. Besides, it could take part in pathogenesis of COPD in various ways and the changes of these items levels is of important values to realize pathosis and therapeutic effect.

  3. Effect of inhalation of Glucocorticoids on the levels of serum NO﹑IL-8 and GM-CSF in Bronchial Asthmatic children%吸入糖皮质激素对支气管哮喘患儿血清NO、IL-8和GM-CSF水平的影响

    Institute of Scientific and Technical Information of China (English)

    温晓春; 蔡爱东

    2014-01-01

    目的:观察支气管哮喘患儿血清IL-6﹑IL-8和GM-CSF水平的变化。方法:采用化学法和放射免疫法分析,先对31例支气管哮喘患儿进行了吸入糖皮质激素前后血清NO﹑IL-8和GM-CSF水平检测,并与35名正常健康儿作比较。结果:支气管哮喘患儿在吸入糖皮质激素前血清NO﹑IL-8和GM-CSF水平均非常显著的高于正常儿组( P<0.01),经吸入糖皮质激素2个月后与正常人比较仍有显著差异( P<0.05)且血清N O水平与I L-8﹑G M-C S F水平呈显著正相关(r=0.5134,0.6012,P<0.01)。结论:吸入糖皮质激素是治疗支气管哮喘的重要手段,其治疗作用与下调NO﹑IL-8和GM-CSF水平有关。%objective: To observe the effect of inhalation of glucocorticoids on the levels of serum NO﹑IL-8 and GM-CSF in Bronchial Asthmatic children. Methods : Serum NO(with chemistry) serum IL-8﹑GM-CSF(with RIA) levels were determined in 31 patients and compared 35 controls. Results: before inhalation of glucocorticoids , the serum NO﹑IL-8 and GM-CSF levels were significantly higher than those in controls(P<0.01).after 2mouths of inhalation of glucocorticoids the serum NO﹑IL-8 and GM-CSF levels though dropped markedly but remained apparently higher than those in controls(P<0.05).Serum NO levels were positively correlated with serum NO﹑IL-8 and GM-CSF levels(r=0.5134,0.6012,P<0.01).Conclusions:Inhalation of glucocorticoids is an important means for bronchial asthma and the therapeutic effects closely related to the down regulation of levels NO﹑IL-8 and GM-CSF.

  4. 乳腺癌患者血清IGF-I、CA153和IL-8水平检测的临床意义%Clinical Significance of Serum Levels of IGF-Ⅰ , CA153 and IL-8 in Patients with Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    林文源; 刘华; 陈琳; 刘蓉华

    2013-01-01

    Objective To explore the clinical significance of serum IGF-Ⅰ,CA153 and IL-8 levels in patients with breast cancer.Methods The serum levels of IGF-Ⅰ,CA153 and IL-8 in 36 patients with breast cancer,40 patients with benign breast patients and 35 healthy controls were determined by RIA and ELISA respectively.Results The serum levels of IGF-Ⅰ,CA153 and IL-8 in patients with breast cancer were significantly higher than those in benign breast patient and controls (P <0.01).The serum levels of IGF-Ⅰ,CA153 and IL-8 in 15 breast cancer patients with lymph node metastasis were significantly higher than those in 21 breast cancer patients without lymph nodes metastasis (P < 0.01).Conclusion The serum levels of IGF-Ⅰ,CA153 and IL-8 might be used as markers in differential diagnosis of malignant from benign diseases,also might be helpful for lymph nodes metastasis prediction.%目的 为探讨乳腺癌患者血清IGF-Ⅰ、CA153和IL-8水平的变化及临床意义.方法 对36例乳腺癌组患者、40例乳腺良性病变组患者和35名正常人,用RIA法和ELISA法分别测定血清IGF-Ⅰ、CA153和IL-8水平.结果 乳腺癌组患者血清IGF-Ⅰ、CA153和IL-8水平均高于乳腺良性病变组患者和正常组,差异有统计学意义(P<0.01);伴有淋巴结转移的乳腺癌患者血清IGF-Ⅰ、CA153和IL-8水平明显高于无淋巴结转移的乳腺癌患者,差异有统计学意义(P<0.01).结论 乳腺癌患者血清IGF-Ⅰ、CA153和IL-8水平的变化可能成为鉴别乳腺良、恶性病变的辅助指标之一,有助于判断乳腺癌有无淋巴结转移及预后.

  5. Chemokines and chemokine receptors in inflammation of the nervous system

    DEFF Research Database (Denmark)

    Huang, D; Han, Yong-Chang; Rani, M R;

    2000-01-01

    This article focuses on the production of chemokines by resident glial cells of the nervous system. We describe studies in two distinct categories of inflammation within the nervous system: immune-mediated inflammation as seen in experimental autoimmune encephalomyelitis (EAE) or multiple sclerosis...

  6. IL-8 inhibits cAMP-stimulated alveolar epithelial fluid transport via a GRK2/PI3K-dependent mechanism

    Science.gov (United States)

    Roux, Jérémie; McNicholas, Carmel M.; Carles, Michel; Goolaerts, Arnaud; Houseman, Benjamin T.; Dickinson, Dale A.; Iles, Karen E.; Ware, Lorraine B.; Matthay, Michael A.; Pittet, Jean-François

    2013-01-01

    Patients with acute lung injury (ALI) who retain maximal alveolar fluid clearance (AFC) have better clinical outcomes. Experimental and small clinical studies have shown that β2-adrenergic receptor (β2AR) agonists enhance AFC via a cAMP-dependent mechanism. However, two multicenter phase 3 clinical trials failed to show that β2AR agonists provide a survival advantage in patients with ALI. We hypothesized that IL-8, an important mediator of ALI, directly antagonizes the alveolar epithelial response to β2AR agonists. Short-circuit current and whole-cell patch-clamping experiments revealed that IL-8 or its rat analog CINC-1 decreases by 50% β2AR agonist-stimulated vectorial Cl− and net fluid transport across rat and human alveolar epithelial type II cells via a reduction in the cystic fibrosis transmembrane conductance regulator activity and biosynthesis. This reduction was mediated by heterologous β2AR desensitization and down-regulation (50%) via the G-protein-coupled receptor kinase 2 (GRK2)/PI3K signaling pathway. Inhibition of CINC-1 restored β2AR agonist-stimulated AFC in an experimental model of ALI in rats. Finally, consistent with the experimental results, high pulmonary edema fluid levels of IL-8 (>4000 pg/ml) were associated with impaired AFC in patients with ALI. These results demonstrate a novel role for IL-8 in inhibiting β2AR agonist-stimulated alveolar epithelial fluid transport via GRK2/PI3K-dependent mechanisms.—Roux, J., McNicholas, C. M., Carles, M., Goolaerts, A., Houseman, B. T., Dickinson, D. A., Iles, K. E., Ware, L. B., Matthay, M. A., Pittet, J.-F. IL-8 inhibits cAMP-stimulated alveolar epithelial fluid transport via a GRK2/PI3K-dependent mechanism. PMID:23221335

  7. Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Fuchigami, Takao [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Kibe, Toshiro [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Koyama, Hirofumi; Kishida, Shosei; Iijima, Mikio [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Nishizawa, Yoshiaki [Kagoshima University Faculty of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Hijioka, Hiroshi; Fujii, Tomomi [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Ueda, Masahiro [Natural Science Centre for Research and Education, Kagoshima University, 1-21-24 Koorimoto, Kagoshima 890-8580 (Japan); Nakamura, Norifumi [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Kiyono, Tohru [Department of Virology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuouku, Tokyo 104-0045 (Japan); Kishida, Michiko, E-mail: kmichiko@m2.kufm.kagoshima-u.ac.jp [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan)

    2014-09-05

    Highlights: • We studied the interaction between tumor cells and fibroblasts in ameloblastoma. • AM-3 ameloblastoma cells secreted significantly high IL-1α levels. • IL-1α derived from AM-3 cells promoted IL-6 and IL-8 secretion of fibroblasts. • IL-6 and IL-8 activated the cellular motility and proliferation of AM-3 cells. - Abstract: Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave

  8. Trefoil Factor-3 (TFF3 Stimulates De Novo Angiogenesis in Mammary Carcinoma both Directly and Indirectly via IL-8/CXCR2.

    Directory of Open Access Journals (Sweden)

    Wai-Hoe Lau

    Full Text Available Mammary carcinoma cells produce pro-angiogenic factors to stimulate angiogenesis and tumor growth. Trefoil factor-3 (TFF3 is an oncogene secreted from mammary carcinoma cells and associated with poor prognosis. Herein, we demonstrate that TFF3 produced in mammary carcinoma cells functions as a promoter of tumor angiogenesis. Forced expression of TFF3 in mammary carcinoma cells promoted proliferation, survival, invasion and in vitro tubule formation of human umbilical vein endothelial cells (HUVEC. MCF7-TFF3 cells with forced expression of TFF3 generated tumors with enhanced microvessel density as compared to tumors formed by vector control cells. Depletion of TFF3 in mammary carcinoma cells by siRNA concordantly decreased the angiogenic behavior of HUVEC. Forced expression of TFF3 in mammary carcinoma cells stimulated IL-8 transcription and subsequently enhanced IL-8 expression in both mammary carcinoma cells and HUVEC. Depletion of IL-8 in mammary carcinoma cells with forced expression of TFF3, or antibody inhibition of IL-8, partially abrogated mammary carcinoma cell TFF3-stimulated HUVEC angiogenic behavior in vitro, as did inhibition of the IL-8 receptor, CXCR2. Depletion of STAT3 by siRNA in MCF-7 cells with forced expression of TFF3 partially diminished the angiogenic capability of TFF3 on stimulation of cellular processes of HUVEC. Exogenous recombinant hTFF3 also directly promoted the angiogenic behavior of HUVEC. Hence, TFF3 is a potent angiogenic factor and functions as a promoter of de novo angiogenesis in mammary carcinoma, which may co-coordinate with the growth promoting and metastatic actions of TFF3 in mammary carcinoma to enhance tumor progression.

  9. Novel effects of the cyclooxygenase-2-selective inhibitor NS-398 on IL-1β-induced cyclooxygenase-2 and IL-8 expression in human ovarian granulosa cells.

    Science.gov (United States)

    Ou, Hui-Ling; Sun, David; Peng, Yen-Chun; Wu, Yuh-Lin

    2016-08-01

    Ovulation is a critical inflammation-like event that is central to ovarian physiology. IL-1β is an immediate early pro-inflammatory cytokine that regulates production of several other inflammatory mediators, such as cyclooxygenase 2 (COX)-2 and IL-8. NS-398 is a selective inhibitor of COX-2 bioactivity and thus this drug is able to mitigate the COX-2-mediated production of downstream prostaglandins and the subsequent inflammatory response. Here we have investigated the action of NS-398 using a human ovarian granulosa cell line, KGN, by exploring IL-1β-regulated COX-2 and IL-8 expression. First, NS-398, instead of reducing inflammation, appeared to further enhance IL-1β-mediated COX-2 and IL-8 production. Using selective inhibitors targeting various signaling molecules, MAPK and NF-κB pathways both seemed to be involved in the impact of NS-398 on IL-1β-induced COX-2 and IL-8 expression. NS-398 also promoted IL-1β-mediated NF-κB p65 nuclear translocation but had no effect on IL-1β-activated MAPK phosphorylation. Flow cytometry analysis demonstrated that NS-398, in combination with IL-1β, significantly enhanced cell cycle progression involving IL-8. Our findings demonstrate a clear pro-inflammatory function for NS-398 in the IL-1β-mediated inflammatory response of granulosa cells, at least in part, owing to its augmenting effect on the IL-1β-induced activation of NF-κB. PMID:27312705

  10. Insulin Like Growth Factor-1 (IGF-1 Causes Overproduction of IL-8, an Angiogenic Cytokine and Stimulates Neovascularization in Isoproterenol-Induced Myocardial Infarction in Rats

    Directory of Open Access Journals (Sweden)

    Nagaraja Haleagrahara

    2011-11-01

    Full Text Available Angiogenesis factors are produced in response to hypoxic or ischemic insult at the site of pathology, which will cause neovascularization. Insulin like growth factor-1 (IGF-1 exerts potent proliferative, angiogenic and anti-apoptotic effects in target tissues. The present study was aimed to evaluate the effects of IGF-1 on circulating level of angiogenic cytokine interleukin-8 (IL-8, in experimentally-induced myocardial ischemia in rats. Male Sprague-Dawley rats were divided into control, IGF-1 treated (2 µg/kg/day subcutaneously, for 5 and 10 days, isoproterenol (ISO treated (85 mg/kg, subcutaneously for two days and ISO with IGF-1 treated (for 5 and 10 days. Heart weight, serum IGF-1, IL-8 and cardiac marker enzymes (CK-MB and LDH were recorded after 5 and 10 days of treatment. Histopathological analyses of the myocardium were also done. There was a significant increase in serum cardiac markers with ISO treatment indicating myocardial infarction in rats. IGF-1 level increased significantly in ISO treated groups and the level of IGF-1 was significantly higher after 10 days of treatment. IL-8 level increased significantly after ISO treatment after 5 and 10 days and IGF-1 concurrent treatment to ISO rats had significantly increased IL-8 levels. Histopathologically, myocyte necrosis and nuclear pyknosis were reduced significantly in IGF-1 treated group and there were numerous areas of capillary sprouting suggestive of neovascularization in the myocardium. Thus, IGF-1 protects the ischemic myocardium with increased production of circulating angiogenic cytokine, IL-8 and increased angiogenesis.

  11. Effect of eradication of Helicobacter pylori on expression levels of FHIT, IL-8 and P73 in gastric mucosa of first-degree relatives of gastric cancer patients.

    Directory of Open Access Journals (Sweden)

    Juan Liao

    Full Text Available Helicobacter pylori (H. pylori infection plays an important role in the carcinogenesis and development of gastric cancer. Eradication of H. pylori can effectively reduce the risk of gastric cancer, but the underlying mechanisms are not fully understood. This study aimed to investigate the effect of eradication of H. pylori on the expression levels of FHIT, IL-8 and P73 in the gastric mucosa of first-degree relatives of gastric cancer patients.One hundred and thirty-two patients with functional dyspepsia having first-degree relatives with gastric cancer were prospectively recruited in this study. Nine patients presented with H. pylori infection and family histories of gastric cancer, 61 with H. pylori infection and without family histories of gastric cancer, 6 without H. pylori infection and with family histories of gastric cancer, and 56 without H. pylori infection and family histories of gastric cancer. The protein and mRNA expression levels of FHIT, IL-8 and P73 in gastric mucosa of the subjects were detected by immunohistochemical staining and polymerase chain reaction, respectively.Compared with the patients without H. pylori infection and family histories of gastric cancer, both the protein and mRNA levels of FIHT significantly decreased in patients with H. pylori infection and/or family histories of gastric cancer, and both the protein and mRNA levels of IL-8 significantly increased. After eradication of H. pylori, both the protein and mRNA levels of FHIT were significantly higher, and both the protein and mRNA levels of IL-8 were significantly lower. However, H. pylori infection and family histories of gastric cancer had no major effect on P73 expression.Down-regulation of FHIT and up-regulation of IL-8 may be involved in the pathogenesis of H. pylori infection in the first-degree relatives of gastric cancer patients.

  12. Trefoil Factor-3 (TFF3) Stimulates De Novo Angiogenesis in Mammary Carcinoma both Directly and Indirectly via IL-8/CXCR2

    Science.gov (United States)

    Lau, Wai-Hoe; Pandey, Vijay; Kong, Xiangjun; Wang, Xiao-Nan; Wu, ZhengSheng; Zhu, Tao; Lobie, Peter E

    2015-01-01

    Mammary carcinoma cells produce pro-angiogenic factors to stimulate angiogenesis and tumor growth. Trefoil factor-3 (TFF3) is an oncogene secreted from mammary carcinoma cells and associated with poor prognosis. Herein, we demonstrate that TFF3 produced in mammary carcinoma cells functions as a promoter of tumor angiogenesis. Forced expression of TFF3 in mammary carcinoma cells promoted proliferation, survival, invasion and in vitro tubule formation of human umbilical vein endothelial cells (HUVEC). MCF7-TFF3 cells with forced expression of TFF3 generated tumors with enhanced microvessel density as compared to tumors formed by vector control cells. Depletion of TFF3 in mammary carcinoma cells by siRNA concordantly decreased the angiogenic behavior of HUVEC. Forced expression of TFF3 in mammary carcinoma cells stimulated IL-8 transcription and subsequently enhanced IL-8 expression in both mammary carcinoma cells and HUVEC. Depletion of IL-8 in mammary carcinoma cells with forced expression of TFF3, or antibody inhibition of IL-8, partially abrogated mammary carcinoma cell TFF3-stimulated HUVEC angiogenic behavior in vitro, as did inhibition of the IL-8 receptor, CXCR2. Depletion of STAT3 by siRNA in MCF-7 cells with forced expression of TFF3 partially diminished the angiogenic capability of TFF3 on stimulation of cellular processes of HUVEC. Exogenous recombinant hTFF3 also directly promoted the angiogenic behavior of HUVEC. Hence, TFF3 is a potent angiogenic factor and functions as a promoter of de novo angiogenesis in mammary carcinoma, which may co-coordinate with the growth promoting and metastatic actions of TFF3 in mammary carcinoma to enhance tumor progression. PMID:26559818

  13. Trefoil Factor-3 (TFF3) Stimulates De Novo Angiogenesis in Mammary Carcinoma both Directly and Indirectly via IL-8/CXCR2.

    Science.gov (United States)

    Lau, Wai-Hoe; Pandey, Vijay; Kong, Xiangjun; Wang, Xiao-Nan; Wu, ZhengSheng; Zhu, Tao; Lobie, Peter E

    2015-01-01

    Mammary carcinoma cells produce pro-angiogenic factors to stimulate angiogenesis and tumor growth. Trefoil factor-3 (TFF3) is an oncogene secreted from mammary carcinoma cells and associated with poor prognosis. Herein, we demonstrate that TFF3 produced in mammary carcinoma cells functions as a promoter of tumor angiogenesis. Forced expression of TFF3 in mammary carcinoma cells promoted proliferation, survival, invasion and in vitro tubule formation of human umbilical vein endothelial cells (HUVEC). MCF7-TFF3 cells with forced expression of TFF3 generated tumors with enhanced microvessel density as compared to tumors formed by vector control cells. Depletion of TFF3 in mammary carcinoma cells by siRNA concordantly decreased the angiogenic behavior of HUVEC. Forced expression of TFF3 in mammary carcinoma cells stimulated IL-8 transcription and subsequently enhanced IL-8 expression in both mammary carcinoma cells and HUVEC. Depletion of IL-8 in mammary carcinoma cells with forced expression of TFF3, or antibody inhibition of IL-8, partially abrogated mammary carcinoma cell TFF3-stimulated HUVEC angiogenic behavior in vitro, as did inhibition of the IL-8 receptor, CXCR2. Depletion of STAT3 by siRNA in MCF-7 cells with forced expression of TFF3 partially diminished the angiogenic capability of TFF3 on stimulation of cellular processes of HUVEC. Exogenous recombinant hTFF3 also directly promoted the angiogenic behavior of HUVEC. Hence, TFF3 is a potent angiogenic factor and functions as a promoter of de novo angiogenesis in mammary carcinoma, which may co-coordinate with the growth promoting and metastatic actions of TFF3 in mammary carcinoma to enhance tumor progression.

  14. IL-8通过上调Bcl-2的表达和下调caspase-3的表达抑制MCF-7乳腺癌细胞凋亡%IL-8 inhibits the apoptosis of MCF-7 human breast cancer cells by up-regulating Bcl-2 and down-regulating caspase-3

    Institute of Scientific and Technical Information of China (English)

    庞雪利; 李矿发; 魏兰; 黄云秀; 苏敏; 王林; 曹红; 陈婷梅

    2015-01-01

    目的 探讨白细胞介素8(IL-8)对乳腺癌细胞MCF-7凋亡的影响及其机制.方法 Westem blot法检测MCF-7细胞IL-8受体CXC趋化因子受体1(CXCR1)、CXCR2的表达;反转录PCR、Western blot法检测(0、20、40、80、160) ng/mL IL-8对MCF-7细胞Bcl-2、caspase-3表达的影响;CCK-8法检测(0、40、80) ng/mL IL-8对MCF-7细胞增殖的影响;相差显微镜下观察80 ng/mL IL-8处理MCF-7后细胞形态的变化;Western blot法检测80 ng/mL IL-8联合信号通路抑制剂10 μmol/L PD980590、10 μmol/L LY294002或50 μmol/L AG490[分别为丝裂原活化蛋白激酶/细胞外调节蛋白激酶(MAPK/ERK)、磷酸肌醇-3激酶/蛋白激酶B(PBK/AKT)、Janus激酶/信号转导子和转录激活子(JAK/STAT)信号通路抑制剂],共同处理MCF-7细胞后,细胞内Bcl-2蛋白表达的变化;Western blot法检测(0、20、40、80、160) ng/mL IL-8对MCF-7细胞磷酸化p-AKT表达的影响;流式细胞术、反转录PCR以及Westem blot法分别检测80 ng/mL IL-8联合10 μmol/L LY294002共同处理MCF-7细胞后,细胞凋亡以及细胞内Bcl-2、caspase-3表达的变化.结果 IL-8受体CXCR1、CXCR2在MCF-7细胞中均有表达;在IL-8的作用下,MCF-7细胞Bcl-2表达升高,caspase-3表达下降,抗凋亡能力明显增强;IL-8能显著上调MCF-7细胞中p-AKT的表达;PBK/AKT信号通路抑制剂LY294002能显著抑制IL-8抗MCF-7细胞凋亡的作用,且减少Bcl-2并增加caspase-3的表达.结论 IL-8可显著抑制MCF-7细胞的凋亡,其机制可能与IL-8激活PI3K/AKT信号通路而上调Bcl-2、下调caspase-3的表达有关.

  15. 白细胞介素-8基因多态性与疾病关系的研究进展%Research Progression of Relationship Between IL-8 Gene Polymorphism and some Diseases

    Institute of Scientific and Technical Information of China (English)

    刘梅; 贺飞燕

    2012-01-01

    白细胞介素-8(IL-8)是一种炎症细胞因子.近年来研究发现,IL-8不同基因型与胃癌、食管癌、乳腺癌、呼吸道合胞病毒感染、哮喘、阿尔茨海默病等疾病相关.本文就近年来国内外有关IL-8基因多态性与上述疾病的关系作一综述.%Interleukin-8 (IL-8) is a kind of inflammatory cells factor. In recent years, IL-8 studies have found that different genotypes related with esophageal and gastric cancer, breast cancer, respiratory syncytial virus infection, Alzheimer's disease and so on. This paper reviewed recent years studies about IL-8 gene polymorphism and relationship of some diseases at home and abroad.

  16. 消化性溃疡病患者治疗前后血清GM-CSF、IL-8和IL-6水平检测的临床意义%Clinical significnce of measurement of changes of sercan GM-CSF、IL-8、IL-6 levels after-crentment in patients with peptic alcer

    Institute of Scientific and Technical Information of China (English)

    漆以芹

    2009-01-01

    Objective To explore the changes of serclm GM-CSF、IL-8 and IL-6 levels both before and after treatment in paticents with peptic ulcer.Metheds Serccm GM-CSF IL-8 and IL-6 levels were measured with RIA in 36 patients with peptic celcer both Before and after treatment as well as in 35 controls.Results Before freatment,the serclun GM-CSF IL-8 and IC-6 levels were significantly higher in the patients than those in the contrels(P0.05).Conclusions Abnormal higher sercun GM-CSF.IL-8 and IL-6 levels played inuportant role in the pathogenesis of peptic ulcer.%目的 探讨了消化性溃疡病患者治疗前后血清GM-CSF、IL-8和IL-6水平的变化及意义.方法 应用放射免疫法对36例消化性溃疡患者进行了血清GM-CSF、IL-8和IL-6水平测定,并与35名正常健康人作比较.结果 消化性溃疡患者在治疗前血清GM-CSF、IC-8和IL-6水平非常显著地高于正常人组(P<0.01),经中西医结合治疗3个月后则与正常人比较无显著性差异(P<0.01),结论 血清GM-CSF、IL-8和IL-6水平异常升高是消化性溃疡病发病的病理因素之一,有重要的临床价值.

  17. Clinical significance of detecting serum levels of TNF-α, IL-10, IL-8 and IL-6 in patients with Breast cancer%乳腺癌患者血清IL-6、IL-8、IL-10和TNF-α的水平变化及临床意义

    Institute of Scientific and Technical Information of China (English)

    王治伟; 迟琼; 万利

    2012-01-01

    目的 探讨乳腺癌患者血清中IL--6、IL-8、IL-10和TNF-α水平与乳腺癌发病的关系.方法 应用放射免疫分析方法检测50例乳腺癌患者不同时期血清IL-6、IL-8、IL-10和TNF-α水平,并与30例正常者对照比较.结果 乳腺癌患者活动期血清中IL-6、IL-8和TNF-α的含量显著高于缓解期和对照组,IL-10含量显著低于缓解期和对照组.缓解期IL-6、IL-8、IL-10和TNF-α含量与对照组比较差异无统计学意义(P>0.05).活动期IL-6、IL-8表达水平与TNF-α呈正相关,与IL-10呈负相关.结论 乳腺癌患者活动期IL-10表达水平降低,IL-6、IL-8和TNF-α 表达水平升高,使体内免疫调节失衡,从而成为乳腺癌患者病因之一.乳腺癌患者血清中IL-6、IL-8、IL-10和TNF-α水平与疾病严重程度显著相关.

  18. High doses of dietary zinc induce cytokines, chemokines, and apoptosis in reproductive tissues during regression.

    Science.gov (United States)

    Sundaresan, N R; Anish, D; Sastry, K V H; Saxena, V K; Nagarajan, K; Subramani, J; Leo, M D M; Shit, N; Mohan, J; Saxena, M; Ahmed, K A

    2008-06-01

    In chickens, high levels of dietary zinc cause molting, and the reproductive system undergoes complete remodeling concomitant to feather replacement. In the present study, the expression profiles of cytokines and chemokines were investigated in the ovary and oviduct of control hens and of hens induced to molt by zinc feeding. The zinc-induced feed-intake suppression, the changes in corticosterone levels, the immune cell populations in the reproductive tract, and the apoptosis of reproductive tissues were analyzed. The expression of mRNAs for interleukin-6 (IL-6), interferon-gamma (IFN-gamma), the avian ortholog of mammalian IL-8 (chCXCLi2), and a chicken MIP-1beta-like chemokine (chCCLi2) in the ovary and of mRNAs for IL-1beta, IL-6, IFN-gamma, transforming growth factor-beta2, chCXCLi2, and chCCLi2 in the oviduct were upregulated significantly during zinc-induced molting. A simultaneous feed-intake reduction was observed with higher expression of cytokines and chemokines. The results of the present investigation also suggested that the upregulation of corticosterone was closely associated with the increased expression of cytokines and chemokines. An increase in apoptosis within reproductive tissue during tissue regression was also noted. We had previously observed the upregulation of these cytokines expression in an earlier study (molting by feed withdrawal). However, the pattern and the level of expression were different among these two methods. These findings indicate that cytokines might be a common mediator of tissue regression during molting induced by diverse methods, although the pattern of induction is different. Thus, a high dose of dietary zinc seems to induce reproductive regression via the upregulation of cytokines and chemokines, the suppression of feed intake, and the increase in serum corticosterone, resulting finally in the apoptosis of reproductive tissues. PMID:18351392

  19. Differential effects of Radix Paeoniae Rubra (Chishao on cytokine and chemokine expression inducible by mycobacteria

    Directory of Open Access Journals (Sweden)

    Li James

    2011-03-01

    Full Text Available Abstract Background Upon initial infection with mycobacteria, macrophages secrete multiple cytokines and chemokines, including interleukin-6 (IL-6, IL-8 and tumor necrosis factor-α (TNF-α, to mediate host immune responses against the pathogen. Mycobacteria also induce the production of IL-10 via PKR activation in primary human monocytes and macrophages. As an anti-inflammatory cytokine, over-expression of IL-10 may contribute to mycobacterial evasion of the host immunity. Radix Paeoniae Rubra (RPR, Chishao, a Chinese medicinal herb with potentials of anti-inflammatory, hepatoprotective and neuroprotective effects, is used to treat tuberculosis. This study investigates the immunoregulatory effects of RPR on primary human blood macrophages (PBMac during mycobacterial infection. Methods The interaction of Bacillus Calmette-Guerin (BCG with PBMac was used as an experimental model. A series of procedures involving solvent extraction and fractionation were used to isolate bioactive constituents in RPR. RPR-EA-S1, a fraction with potent immunoregulatory effects was obtained with a bioactivity guided fractionation scheme. PBMac were treated with crude RPR extracts or RPR-EA-S1 before BCG stimulation. The expression levels of IL-6, IL-8, IL-10 and TNF-α were measured by qPCR and ELISA. Western blotting was used to determine the effects of RPR-EA-S1 on signaling kinases and transcriptional factors in the BCG-activated PBMac. Results In BCG-stimulated macrophages, crude RPR extracts and fraction RPR-EA-S1 specifically inhibited IL-10 production while enhanced IL-8 expression at both mRNA and protein levels without affecting the expressions of IL-6 and TNF-α. Inhibition of BCG-induced IL-10 expression by RPR-EA-S1 occurred in a dose- and time-dependent manner. RPR-EA-S1 did not affect the phosphorylation of cellular protein kinases including MAPK, Akt and GSK3β. Instead, it suppressed the degradation of IκBα in the cytoplasm and inhibited the

  20. The cell wall component lipoteichoic acid of Staphylococcus aureus induces chemokine gene expression in bovine mammary epithelial cells

    Science.gov (United States)

    KIKU, Yoshio; NAGASAWA, Yuya; TANABE, Fuyuko; SUGAWARA, Kazue; WATANABE, Atsushi; HATA, Eiji; OZAWA, Tomomi; NAKAJIMA, Kei-ichi; ARAI, Toshiro; HAYASHI, Tomohito

    2016-01-01

    Staphylococcus aureus (SA) is a major cause of bovine mastitis, but its pathogenic mechanism remains poorly understood. To evaluate the role of lipoteichoic acid (LTA) in the immune or inflammatory response of SA mastitis, we investigated the gene expression profile in bovine mammary epithelial cells stimulated with LTA alone or with formalin-killed SA (FKSA) using cap analysis of gene expression. Seven common differentially expressed genes related to immune or inflammatory mediators were up-regulated under both LTA and FKSA stimulations. Three of these genes encode chemokines (IL-8, CXCL6 and CCL2) functioning as chemoattractant molecules for neutrophils and macrophages. These results suggest that the initial inflammatory response of SA infection in mammary gland may be related with LTA induced chemokine genes. PMID:27211287

  1. Expressions of IL-6 and IL-8 in normal gastric tissue, gastric ulcer and gastric cancer%IL-6和IL-8在正常胃组织、胃溃疡及胃癌组织中的表达

    Institute of Scientific and Technical Information of China (English)

    赵志威; 朴大勋; 姜涛; 张哲男; 王剑冰; 荆琼优

    2014-01-01

    目的 探讨白细胞介素(IL)-6和IL-8在正常胃组织、胃溃疡及胃癌组织中的表达情况.方法 采用酶联免疫吸附法(ELISA)测定正常对照组(33例)、胃溃疡患者(30例)和准备手术的胃癌患者(52例)血浆中IL-6和IL-8的表达水平,并随访胃癌患者术后1周的IL-6、IL-8表达水平;免疫组织化学法检测胃癌周围正常组织(45例)、胃溃疡组织(35例)和胃癌组织(45例)标本中IL-6和IL-8的表达.结果 胃癌患者(术前和术后)血浆中IL-6、IL-8的表达明显高于胃溃疡和正常对照组(均P<0.0l),胃癌患者术后IL-6和IL-8水平较术前明显降低(P<0.01).癌周正常组织、胃溃疡和胃癌组织中IL-6和IL-8蛋白阳性表达率依次上升,且差异有统计学意义(x2=38.87,P<0.01;x2=42.23,P<0.01).结论 IL-6和IL-8在胃癌患者血浆和胃癌组织中均表达上调,检测患者血浆和病理组织中的IL-6、IL-8水平有助于判断病情和评估预后.

  2. Clinical Significance of Measurement of Serum hs-CRP,IL-8 and IL-10 Levels in Patients with Periodontitis%牙周病患者血清hs-CRP、IL-8和IL-10检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    王惠

    2012-01-01

    Objective To explore the significance of changes on serum hs-CRP,IL-8 and IL-10 levels in patients with periodonti-tis. MethOtS Serum hs-CRP(with immuno-turbidimetry) ,IL-8 (with RIA) ,IL-10 (with ELISA) levels were measured in 32 patients with periodontitis both before and after treatment as well as in 35 normal controls. Results Before treatment serum levels of hs-CRP, IL-8 and IL-10 were extremely higher in the patients than those in controls (P<0.01). After one month of treatment, the serum hs-CRP,IL-8 and IL-10 levels decreased but still significantly higher than those in controls (P <0.05 ) Conclusion Determination of Changes of serum hs-CRP,IL-8 and IL-10 levels has definite value to study pathogenesis, prevention and guide the therapeutic effect in patients with periodontitis.%目的:探讨牙周病患者血清hs-CRP、IL-8和IL-10水平的变化及临床意义.方法:应用放射免疫分析、酶联法和免疫比浊法对32例牙周病患者进行了血清hs-CRP、IL-8和IL-10检测,并与35名正常人作比较.结果:牙周病患者在治疗前血清hs-CRP、IL-8和IL-10水平均非常显著地高于正常人组(P<0.01),经治疗1个月后与正常人组比较仍有显著性差异(P<0.05).结论:检测血清hs-CRP、IL-8和IL-10水平的变化,对探讨牙周病发病机制、预防和指导治疗均有一定的临床价值.

  3. The study of the relationship between Helicobacter pylori CagA and VacA genotype and IL-6, IL-8%幽门螺杆菌CagA和VacA基因型与IL-6、IL-8的关系研究

    Institute of Scientific and Technical Information of China (English)

    郭皓; 戚艳丽; 张世同; 李慧; 金建军

    2016-01-01

    目的 观察幽门螺杆菌(Helicobacter pylori,H.pylori)的不同基因型与IL-6、IL-8之间的关系,了解H.pylori的致病机制.方法 采集91例经14C尿素呼气试验检测为H.pylori(+)患者血清,采用酶联免疫吸附试验(ELISA)对CagA、VacA进行定性分析,对IL-6、IL-8进行定量分析.结果 CagA(+)与CagA(-)中所含IL-6、IL-8含量差异有统计学意义(=6.55、t=7.348,P<0.001);VacA(+)与VacA(-)中所含IL-6、IL-8含量差异有统计学意义(t=6.418、t=6.977,P<0.001);CagA、VacA均阳性中所含IL-6、IL-8的含量较CagA、VacA均阴性差异有统计学意义(=6.438、t=7.231,P<0.001);CagA阳性患者血清中IL-6与IL-8含量呈正相关(r=0.672,P<0.01),VacA阳性患者血清中IL-6与IL-8含量呈正相关(r=0.664,P<0.01).结论 CagA、VacA基因型与IL-6、IL-8之间有密切关系,IL-6、IL-8在H.pylori的致病机制中起重要作用,细胞因子在H.pylori感染诱导的炎症反应涉及多种细胞及多种细胞因子的相互作用.

  4. Clinical Significance of Determination of Changes of Serum TNF-α, IL-6 and IL-8 Levels After Treatment in Patients with Chronic Prostatitis%慢性前列腺炎患者治疗前后血清TNF-α、IL-6和IL-8检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    孟晓波

    2008-01-01

    目的:探讨了慢性前列腺炎患者治疗前后血清TNF-α、IL-6和IL-8水平的变化及意义.方法:应用放射免疫分析对42例慢性前列腺炎患者进行了血清TNF-α、IL-6和IL-8检测,并与35名正常健康人作比较.结果:慢性前列腺炎患者在治疗前血清TNF-α、IL-6和IL-8水平均非常显著地高于正常人组(P<0.01),经综合治疗后2周,除TNF-α水平与正常人比较无差异外,血清IL-6和IL-8水平与正常人比较仍有显著性差异(P<0.05).结论:血清TNF-α、IL-6和IL-8可能以不同的方式参与了慢性前列腺炎的发病,其检测对了解病情、指导治疗具有重要的临床价值.

  5. Clinical Significance of Measurement the Changes on Serum IL-2, IL-8, IL-18 and VEGF Levels After Treatment in Patients with Acute Cerebral Infarction%ACI患者治疗前后血清IL-2、IL-8、IL-18和VEGF检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    张春雷; 章红梅

    2013-01-01

    目的:探讨了急性脑梗死(ACI)患者治疗前后血清IL-2、IL-8、IL-18和VEGF水平的变化及临床意义.方法:应用放射免疫分析、酶联法对33例ACI患者进行了治疗前后血清IL-2、IL-8、IL-18和VEGF检测,并与35名正常健康人作比较.结果:ACI患者在治疗前血清IL-8、IL-18和VEGF水平非常显著地高于正常人组(P<0.01),而血清IL-2水平又非常显著地低于正常人组(P<0.01),经治疗3个月后与正常人组比较仍有显著性差异(P<0.05).且血清IL-2水平与IL-8、IL-18和VEGF水平呈显著负相关(r=-0.4218、-0.4726、-0.5014,P<0.01).结论:ACI的发生、发展与血清IL-2、IL-8、IL-18和VEGF水平密切相关.

  6. Clinical significance of detection of serum interleukin(IL-6),tumr necrosis factor and urine IL-6 and IL-8 levels in patients with hepatocirrhosis%肝硬化患者血清IL-6、TNF和尿液IL-6、IL-8检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    周彦

    2001-01-01

    目的探讨细胞因子在肝硬化发病中的作用.方法采用双抗体夹心Elisa法对54例肝硬化患者和35例正常人血清白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)和尿液IL-6、IL-8进行检测.结果肝硬化患者血清中IL-6、TNF和尿液IL-6、IL-8含量较对照组明显升高(P<0.01),血IL-6、TNF含量GN与尿液量白蛋白呈高度正相关:尿液IL-6、IL-8呈显著正相关(r=0.5728,P<0.05).结论肝硬化患者病程中TNF、IL-6、IL-8均处于高活性状态,IL-6与体液免疫反应亢进所致的免疫病理损伤有关,IL-6、IL-8、TNF参与肾脏的免疫损伤、可作为判定患者预后和转归指标.

  7. COPD患者治疗前后血清hs-CRP、TNF-α、IL-6、IL-8检测的临床意义%Clinical Significance of Determination of Serum hs-CRP, TNF-α, IL-6 and IL-8 Levels After Treatment in Patients with Chronic Obstructive Pulmonary Disease

    Institute of Scientific and Technical Information of China (English)

    胡蓉

    2007-01-01

    目的:探讨慢性阻塞性肺疾病(COPD)患者治疗前后血清hs-CRP、TNF-α、IL-6、IL-8水平的变化及意义.方法:应用放免法和免疫比浊法对46例COPD患者进行治疗前后血清hs-CRP、TNF-α、IL-6、IL-8检测,并与35名正常健康人作比较.结果:COPD患者在治疗前血清hs-CRP、TNF-α、IL-6、IL-8水平均非常显著地高于正常人组(P<0.01),综合治疗后2周,除hs-CRP水平与正常人比较无差异外,TNF-α、IL-6、IL-8水平与正常人组比较仍有显著性差异(P<0.05).结论:hs-CRP、TNF-α、IL-6、IL-8可能以不同的方式参与了COPD的发病,其水平的检测对于了解病情、指导治疗具有重要的临床价值.

  8. Lycopene inhibits NF-kB-mediated IL-8 expression and changes redox and PPARγ signalling in cigarette smoke-stimulated macrophages.

    Directory of Open Access Journals (Sweden)

    Rossella E Simone

    Full Text Available Increasing evidence suggests that lycopene, the major carotenoid present in tomato, may be preventive against smoke-induced cell damage. However, the mechanisms of such a prevention are still unclear. The aim of this study was to investigate the role of lycopene on the production of the pro-inflammatory cytokine IL-8 induced by cigarette smoke and the possible mechanisms implicated. Therefore, human THP-1 macrophages were exposed to cigarette smoke extract (CSE, alone and following a 6-h pre-treatment with lycopene (0.5-2 µM. CSE enhanced IL-8 production in a time- and a dose-dependent manner. Lycopene pre-treatment resulted in a significant inhibition of CSE-induced IL-8 expression at both mRNA and protein levels. NF-kB controlled the transcription of IL-8 induced by CSE, since PDTC prevented such a production. Lycopene suppressed CSE-induced NF-kB DNA binding, NF-kB/p65 nuclear translocation and phosphorylation of IKKα and IkBα. Such an inhibition was accompanied by a decrease in CSE-induced ROS production and NOX-4 expression. Lycopene further inhibited CSE-induced phosphorylation of the redox-sensitive ERK1/2, JNK and p38 MAPKs. Moreover, the carotenoid increased PPARγ levels which, in turn, enhanced PTEN expression and decreased pAKT levels in CSE-exposed cells. Such effects were abolished by the PPARγ inhibitor GW9662. Taken together, our data indicate that lycopene prevented CSE-induced IL-8 production through a mechanism involving an inactivation of NF-kB. NF-kB inactivation was accompanied by an inhibition of redox signalling and an activation of PPARγ signalling. The ability of lycopene in inhibiting IL-8 production, NF-kB/p65 nuclear translocation, and redox signalling and in increasing PPARγ expression was also found in isolated rat alveolar macrophages exposed to CSE. These findings provide novel data on new molecular mechanisms by which lycopene regulates cigarette smoke-driven inflammation in human macrophages.

  9. The Role of Cytokines, Chemokines, and Growth Factors in the Pathogenesis of Pityriasis Rosea

    Directory of Open Access Journals (Sweden)

    Francesco Drago

    2015-01-01

    Full Text Available Introduction. Pityriasis rosea (PR is an exanthematous disease related to human herpesvirus- (HHV- 6/7 reactivation. The network of mediators involved in recruiting the infiltrating inflammatory cells has never been studied. Object. To investigate the levels of serum cytokines, growth factors, and chemokines in PR and healthy controls in order to elucidate the PR pathogenesis. Materials and Methods. Interleukin- (IL- 1, IL-6, IL-17, interferon- (IFN- γ, tumor necrosis factor- (TNF- α, vascular endothelial growth factor (VEGF, granulocyte colony stimulating factor (G-CSF, and chemokines, CXCL8 (IL-8 and CXCL10 (IP-10, were measured simultaneously by a multiplex assay in early acute PR patients’ sera and healthy controls. Subsequently, sera from PR patients were analysed at 3 different times (0, 15, and 30 days. Results and discussion. Serum levels of IL-17, IFN-γ, VEGF, and IP-10 resulted to be upregulated in PR patients compared to controls. IL-17 has a key role in host defense against pathogens stimulating the release of proinflammatory cytokines/chemokines. IFN-γ has a direct antiviral activity promoting NK cells and virus specific T cells cytotoxicity. VEGF stimulates vasculogenesis and angiogenesis. IP-10 can induce chemotaxis, apoptosis, cell growth, and angiogenesis. Conclusions. Our findings suggest that these inflammatory mediators may modulate PR pathogenesis in synergistic manner.

  10. Chemokines in tumor development and progression

    Energy Technology Data Exchange (ETDEWEB)

    Mukaida, Naofumi, E-mail: naofumim@kenroku.kanazawa-u.ac.jp [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192 (Japan); Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Chiyoda-ku, Tokyo 102-0075 (Japan); Baba, Tomohisa [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192 (Japan)

    2012-01-15

    Chemokines were originally identified as mediators of the inflammatory process and regulators of leukocyte trafficking. Subsequent studies revealed their essential roles in leukocyte physiology and pathology. Moreover, chemokines have profound effects on other types of cells associated with the inflammatory response, such as endothelial cells and fibroblasts. Thus, chemokines are crucial for cancer-related inflammation, which can promote tumor development and progression. Increasing evidence points to the vital effects of several chemokines on the proliferative and invasive properties of tumor cells. The wide range of activities of chemokines in tumorigenesis highlights their roles in tumor development and progression.

  11. 热化疗治疗非小细胞肺癌对IL-2、IL-6、IL-8、IL-10及TNF的影响%Effect of thermochemotherapy on levels of IL-2 ,IL-6 ,IL-8 ,IL-10 and TNF in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    李新民; 尉继伟; 刘治邦; 刘建国

    2014-01-01

    目的 探讨热化疗治疗非小细胞肺癌(NSCLC)对白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、白细胞介素-10(IL-10)及肿瘤坏死因子(TNF)的影响.方法 回顾性分析大同大学附属医院2004年10月至2013年1月收治的134例NSCLC患者,进行热疗联合NP方案化疗(NVB+ DDP),并分别在治疗前、治疗3个周期后、治疗6个周期后、治疗结束后3个月对患者血清中IL-2、IL-6、IL-8、IL-10及TNF的变化进行监测.结果 热化疗3个周期后,IL-2、TNF水平逐渐增高,明显高于治疗前;IL-6、IL-8和IL-10水平明显低于化疗前.热化疗6个周期后,血IL-6、IL-8、IL-10、IL-2和TNF都有所下降,其中IL-2、TNF浓度显著低于化疗3个周期后的水平.热化疗结束后3个月,血IL-6、IL-8、IL-10水平继续下降;而IL-2、TNF浓度逐渐增高,低于化疗3个周期后的水平,但高于治疗前水平.结论 热化疗治疗NSCLC对IL-2、TNF水平有明显的增高作用,而对IL-6、IL-8、IL-10有降低作用.%Objective To investigate the effect of hot therapy on interleukin-2 (IL-2),interleukin-6 (IL-6),interlerukin-8 (IL-8),interleukin-10 (IL-10) and tumor necrosis factor (TNF) in nonsmall cell lung cancer(NSCLC).Methods One hundred and thirty-four patients with NSCLC,admitted to our hospital from October 2004 to January 2013,received hot therapy and vinorelbine plus cisplatin (NP) chemotherapy.The IL-6,IL-8,IL-10 and TNF level before therapy,after 3 cycles,after 6 cycles and 3 months after chemotherapy were observed.Results IL-2 and TNF levels increased gradually after 3 cycles of hot therapy,and were significant higher than those before therapy.Compared to before therapy,IL-6,IL-8 and IL-10 levels significantly decreased.IL-6,IL-8,IL-10,IL-2 and TNF levels all decreased at 6 months after hot therapy.IL-2 and TNF levels were significant lowered than those of 3 cycles after chemotherapy.IL-6,IL-8 and IL-10 continued to decrease 3 months after the end of

  12. The expression of lysophosphatidic acid, its receptors, and IL-6 and IL-8 in breast cancer%溶血磷脂酸及其受体和IL-6 IL-8在乳腺癌进展中的表达变化与意义

    Institute of Scientific and Technical Information of China (English)

    涂福平; 黄莉; 王祥财; 许明君; 王钇力; 衷敬华

    2013-01-01

    Objective:This work aimed to investigate the expression level of lysophosphatidic acid (LPA) and its receptors. The paper also discussed the interrelationship among the LPA, the receptors, and IL-6 and IL-8 in breast cancer tissues. Methods:The ex-pressions of the 3 hypo-types of LPA receptor in the breast cancer and paraneoplastic tissues were detected using semi-quantitative re-verse transcription polymerase chain reaction. The plasma levels of LPA, IL-6 and IL-8 were respectively detected in healthy subjects and in patients with benign breast tumor using the LPA biochemistry and enzyme linked immunosorbent assay kits. Results:The plas-ma LPA level was significantly higher in patients with breast cancer metastasis than in those with local breast cancer (P<0.01), benign breast tumor (P<0.01), and healthy volunteers (P<0.01). In addition, the IL-6 and IL-8 plasma levels were higher in the group with me-tastasis compared with the other three groups, too (P<0.01). LPA1 expression level was higher in breast cancer tissue than in benign breast tumor (P<0.05) and in normal breast tissue (P<0.05). There was a significantly positive correlation between the plasma LPA and the plasma IL-6 in patients with breast cancer (P<0.01), and between the plasma LPA and IL-8 (P<0.01). Conclusion:LPA expressions on the endogenous IL-6 and IL-8 in patients with breast cancer may have an up-regulation. Moreover, the detection of the LPA, IL-6, and IL-8 expression levels may have some predictable effects on metastatic breast cancer, especially bone metastases.%  目的:探讨溶血磷脂酸(lysophosphatidic acid,LPA)及其受体和IL-6与IL-8在乳腺癌进展中的表达及临床意义。方法:采用半定量RT-PCR方法检测乳腺肿瘤组织和瘤旁组织中LPA受体的表达水平。采用LPA生化测定法和酶联免疫吸附(ELISA)法分别检测乳腺肿瘤患者和健康妇女的血浆LPA、IL-6和IL-8水平。结果:术后复发转

  13. Isolation and identification of Malassezia species from Chinese and Korean patients with seborrheic dermatitis and in vitro studies on their bioactivity on sebaceous lipids and IL-8 production.

    Science.gov (United States)

    Kim, Soo Young; Kim, Se Hyun; Kim, Su Na; Kim, Ah-Reum; Kim, Yu Ri; Kim, Min Jung; Park, Won-Seok; Lee, John Hwan; Jung, Won Hee; Lee, Yang Won; Choe, Yong Beom; Ahn, Kyu Joong

    2016-05-01

    We investigated the distribution of Malassezia yeast in 120 Chinese (20 patients from each of six cities) and 20 Korean patients with scalp seborrheic dermatitis (SD) and dandruff (SD/D) using ITS1 and ITS2 polymerase chain reaction-restriction fragment length polymorphism. Bioactivity was studied by quantifying sebum lipid production by human primary sebocytes and inflammatory cytokine, interleukin-8 (IL-8) production was studied by exposing HaCaT keratinocytes with extracts of five standard Malassezia strains; M. globosa, M. restricta, M. sympodialis, M. dermatis and M. slooffiae. M. restricta and M. globosa were the most frequently encountered species from both Chinese and Korean patients. These two Malassezia species also promoted neutral lipid synthesis although the result was not statistically significant and induced significant increase in IL-8 production among the five Malassezia species studied. The study suggests a possible role of these organisms in the pathogenesis of SD/D. PMID:26786542

  14. 血清CA15-3、IL-8水平与乳腺癌骨转移关系的探讨%Study on the Relationship Between Serum CA15 -3, IL-8, Levels and Bone Metastasis in Patients with Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    谭维琴; 杨士军; 鲍艳梅

    2007-01-01

    目的:为探讨乳腺癌患者血清CA15-3、IL-8水平与骨转移的关系.方法:对83例乳腺癌手术后患者分别检测血清CA15-3、白介素8(IL-8)和行99mTc-MDP全身骨显像,进行对比分析.结果:乳腺癌无骨转移组血清CA15-3、IL-8水平与正常对照组比较无明显差异(P>0.05);乳腺癌伴骨转移组患者血清CA15-3、IL-8水平明显升高,与乳腺癌无骨转移组及对照组比较均有统计学意义(P<0.01).结论:CA15-3对于预测乳腺癌骨转移、筛选行全身骨显像病人和降低骨显像的误诊具有重要意义;IL-8参与乳腺癌骨转移的发生和发展过程,检测IL-8等细胞因子水平对于乳腺癌骨转移的病理研究和预防、治疗可能具有重要价值.

  15. 乳腺癌患者手术前后血清IL-6、IL-8和VEGF-A水平变化及临床意义%Clinical significance of level changes of serum IL-6, IL-8 and VEGF-A in patients with breast cancer before and after operations

    Institute of Scientific and Technical Information of China (English)

    陈坤; 王晓刚; 李狄航; 孔勇

    2014-01-01

    目的 探讨乳腺癌患者手术前后血清白细胞介素-6(IL-6)、IL-8和血管内皮生长因子-A (VEGF-A)水平变化及其临床意义.方法 42例乳腺癌患者根据不同临床分期采取改良根治术或保乳术治疗,分别检测健康体检者和乳腺癌患者手术前3d、术后7d血清IL-6、IL-8和VEGF-A水平.结果 乳腺癌患者术前血清IL-6、IL-8和VEGF-A水平均高于对照组(P<0.01),术后各期乳腺患者血清IL-6、IL-8和VEGF-A水平均显著下降(P< 0.05或P<0.01).不同分期乳腺癌患者组间比较,血清IL-6、IL-8和vEGF-A水平差异均具有统计学意义(P<0.05).结论 乳腺癌患者体内IL-6、IL-8和VEGF-A水平存在高表达,且在一定程度上影响疾病发展,及时检测并诊断该类因子水平有助于了解乳腺癌患者疾病发展和预后.

  16. Effect of two kinds of porcelain crown on AST, ALP, TNF-α, IL-8, GP-x and MDA levels in gingival crevicular fluid

    Institute of Scientific and Technical Information of China (English)

    Ya-Ling Wang; Zhi Cao; Shi-Xia Zhan

    2016-01-01

    Objective:To investigate the effect of two kinds of porcelain crown on AST, ALP, TNF-α, IL-8, GP-x and MDA levels in gingival crevicular fluid.Methods: A total of 80 patients with dental porcelain crowns at front teeth during February 2013 to February 2016 were randomly divided into cobalt-chromium alloy PFM group (n=40) and gold alloy PFM group (n=40). After 6 months, the amount of gingival crevicular fluid, GI, PD, AST, ALP, TNF-α, IL-8, GP-x and MDA levels in gingival crevicular fluid were recorded and analyzed.Results: There were no differences in amount of gingival crevicular fluid, GI and PD before treatment of the two groups (P>0.05). After treatment, the amount of gingival crevicular fluid, GI and PD of the two groups were significantly higher than before treatment (P0.05). After treatment, the AST, ALP, TNF-α, IL-8 and MDA levels in gingival crevicular fluid of the two groups were significantly higher than before treatment (P<0.05), but that of the gold alloy PFM group were significantly lower than cobalt-chromium alloy PFM group (P<0.05). After treatment, the GP-x level in gingival crevicular fluid of the two groups were significantly lower than before treatment (P<0.05), but that of the gold alloy PFM group were significantly higher than cobalt-chromium alloy PFM group (P<0.05).Conclusions:Gold alloy PFM can significantly reduce the AST, ALP, TNF-α, IL-8 and MDA levels in gingival crevicular fluid, improve the GP-x level in gingival crevicular fluid, shows better biocompatibility and clinical outcomes than cobalt-chromium alloy PFM.

  17. Baicalin downregulates Porphyromonas gingivalis lipopolysaccharide-upregulated IL-6 and IL-8 expression in human oral keratinocytes by negative regulation of TLR signaling.

    Directory of Open Access Journals (Sweden)

    Wei Luo

    Full Text Available Periodontal (gum disease is one of the main global oral health burdens and severe periodontal disease (periodontitis is a leading cause of tooth loss in adults globally. It also increases the risk of cardiovascular disease and diabetes mellitus. Porphyromonas gingivalis lipopolysaccharide (LPS is a key virulent attribute that significantly contributes to periodontal pathogenesis. Baicalin is a flavonoid from Scutellaria radix, an herb commonly used in traditional Chinese medicine for treating inflammatory diseases. The present study examined the modulatory effect of baicalin on P. gingivalis LPS-induced expression of IL-6 and IL-8 in human oral keratinocytes (HOKs. Cells were pre-treated with baicalin (0-80 µM for 24 h, and subsequently treated with P. gingivalis LPS at 10 µg/ml with or without baicalin for 3 h. IL-6 and IL-8 transcripts and proteins were detected by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The expression of nuclear factor-κB (NF-κB, p38 mitogen-activated protein kinase (MAPK and c-Jun N-terminal kinase (JNK proteins was analyzed by western blot. A panel of genes related to toll-like receptor (TLR signaling was examined by PCR array. We found that baicalin significantly downregulated P. gingivalis LPS-stimulated expression of IL-6 and IL-8, and inhibited P. gingivalis LPS-activated NF-κB, p38 MAPK and JNK. Furthermore, baicalin markedly downregulated P. gingivalis LPS-induced expression of genes associated with TLR signaling. In conclusion, the present study shows that baicalin may significantly downregulate P. gingivalis LPS-upregulated expression of IL-6 and IL-8 in HOKs via negative regulation of TLR signaling.

  18. Vascular and inflammatory high fat meal responses in young healthy men; a discriminative role of IL-8 observed in a randomized trial.

    Directory of Open Access Journals (Sweden)

    Diederik Esser

    Full Text Available BACKGROUND: High fat meal challenges are known to induce postprandial low-grade inflammation and endothelial dysfunction. This assumption is largely based on studies performed in older populations or in populations with a progressed disease state and an appropriate control meal is often lacking. Young healthy individuals might be more resilient to such challenges. We therefore aimed to characterize the vascular and inflammatory response after a high fat meal in young healthy individuals. METHODS: In a double-blind randomized cross-over intervention study, we used a comprehensive phenotyping approach to determine the vascular and inflammatory response after consumption of a high fat shake and after an average breakfast shake in 20 young healthy subjects. Both interventions were performed three times. RESULTS: Many features of the vascular postprandial response, such as FMD, arterial stiffness and micro-vascular skin blood flow were not different between shakes. High fat/high energy shake consumption was associated with a more pronounced increase in blood pressure, heart rate, plasma concentrations of IL-8 and PBMCs gene expression of IL-8 and CD54 (ICAM-1, whereas plasma concentrations of sVCAM1 were decreased compared to an average breakfast. CONCLUSION: Whereas no difference in postprandial response were observed on classical markers of endothelial function, we did observe differences between consumption of a HF/HE and an average breakfast meal on blood pressure and IL-8 in young healthy volunteers. IL-8 might play an important role in dealing with high fat challenges and might be an early marker for endothelial stress, a stage preceding endothelial dysfunction.

  19. Activation of Coagulation by Administration of Recombinant Factor VIIa Elicits Interleukin 6 (IL-6) and IL-8 Release in Healthy Human Subjects

    OpenAIRE

    de Jonge, Evert; Friederich, Philip W.; Vlasuk, George P.; Rote, William E.; Vroom, Margaretha B.; Levi, Marcel; van der Poll, Tom

    2003-01-01

    The activation of coagulation has been shown to contribute to proinflammatory responses in animal and in vitro experiments. Here we report that the activation of coagulation in healthy human subjects by the administration of recombinant factor VIIa also elicits a small but significant increase in the concentrations of interleukin 6 (IL-6) and IL-8 in plasma. This increase was absent when the subjects were pretreated with recombinant nematode anticoagulant protein c2, the inhibitor of tissue f...

  20. African Dust Storms Reaching Puerto Rican Coast Stimulate the Secretion of IL-6 and IL-8 and Cause Cytotoxicity to Human Bronchial Epithelial Cells (BEAS-2B).

    Science.gov (United States)

    Rodríguez-Cotto, Rosa I; Ortiz-Martínez, Mario G; Rivera-Ramírez, Evasomary; Méndez, Loyda B; Dávila, Julio C; Jiménez-Vélez, Braulio D

    2013-10-01

    African dust storm events (ADE) travel across the Atlantic Ocean (ADEAO) and reach the Puerto Rican coast (ADEPRC), potentially impacting air quality and human health. To what extent seasonal variations in atmospheric particulate matter (PM) size fractions, composition and sources trigger respiratory-adverse effects to Puerto Ricans is still unclear. In the present study, we investigated the pro-inflammatory and cytotoxic effects of PM samples harvested during ADEAO (PM10), ADEPRC (PM2.5 and PM10) and Non-ADE (Preand Post-ADEAO and Non-ADEPRC), using BEAS-2B cells. Endotoxins (ENX) in PM2.5 and PM10 extracts and traces of metals (TMET) in PM2.5 extracts were also examined. IL-6 and IL-8 secretion and cytotoxicity were used as endpoints. ADEAO and ADEPRC extracts were found to be more cytotoxic than Non-ADE and ADEAO were more toxic than ADEPRC extracts. PM10 extracts from ADEAO and Post-ADEAO caused significant secretion of IL-8. IL-6 and IL-8 secretion was higher following treatment with PM10 and PM2.5 ADEPRC than with Non-ADEPRC extracts. ENX levels were found to be higher in PM10 ADEAO than in the rest of the samples tested. TMET levels were higher in PM2.5 ADEPRC than in Non-ADEPRC extracts. Deferoxamine significantly reduced cytotoxicity and IL-6 and IL-8 secretion whereas Polymyxin B did not. TMET in PM2.5 fractions is a major determinant in ADEPRC-induced toxicity and work in conjunction with ENX to cause toxicity to lung cells in vitro. ENX and TMET may be responsible, in part, for triggering PM-respiratory adverse responses in susceptible and predisposed individuals. PMID:25002916

  1. The Effect of Montelukast on the Levels of IL-6,IL-8 and IL-10 in Patients with Bronchial Asthma%孟鲁司特对支气管哮喘患者血清IL-6、IL-8和IL-10水平的影响

    Institute of Scientific and Technical Information of China (English)

    许成

    2012-01-01

    Objective To explore the effect of Montelukaat on serum IL-6,IL-8 and IL-10 levels in patients with bronchial asthma. Methods Serum TL-6,TLS (with RIA) ,IL-10 (with ELISA) levels were measured in 31 patients after Montelukast treatment with bronchial asthma as well as in 35 normal healthy controls. Result Before treatment serum IL-6, IL-8 levels in the asthma group were significantly higher than those in controls (P<0.01). While the IL-10 level was undoubtedly lower than that in the controls (P <0.01). After treatment, the serum IL-6, IL-8 and IL-10 levels were still significantly (P<0.05). Conclusion Montelukast treatment could bring about some regulatory effect on serum IL-6, IL-8 and IL-10 levels in patients with asthma and furthermore reducing the severity of inflammation and enhancing remission.%目的 探讨孟鲁司特在支气管哮喘患者体内IL-6、IL-8和IL-10水平的影响.方法 应用放射免疫分析和酶联法对31例支气管哮喘患者应用孟鲁司特治疗前后血清IL-6、IL-8和IL-10水平的变化,并与35名正常健康人作比较.结果 支气管哮喘患者在治疗前血清IL-6、IL-8水平非常显著地高于正常人组(P<0.01),而IL-10水平显著地低于正常人组(P<0.01),经治疗2周后与正常人组比较仍有显著性差异(P<0.05).结论 孟鲁司特对支气管哮喘患者血清IL-6、IL-8和IL-10有一定程度的调节作用,从而降低患者体内的炎症水平,促进病情缓解和好转.

  2. NKG2D、MICA和IL-8在早期自然流产组织中的表达及意义%Expression and implication of NKG2D, MICA, and IL-8 in villi and decidua of spontaneous abortus at first trimester

    Institute of Scientific and Technical Information of China (English)

    赵之明; 刘福民; 刘小云; 朱学文; 万美容; 冯霞

    2012-01-01

    目的 探讨NKG2D、MICA和IL-8在早期自然流产(ESA)患者蜕膜绒毛中的表达及其意义.方法 选取20例ESA患者作为流产组,20例正常早孕人工流产妇女作为对照组,RT-PCR和Western Blotting法检测两组蜕膜绒毛组织中NKG2D、MICA和IL-8 mRNA及蛋白的表达,免疫组织化学法检测蜕膜绒毛组织中MICA蛋白的表达,分析NKG2D、MICA与IL-8之间的相关性.结果 流产组蜕膜绒毛组织中NKG2D、MICA和IL-8 mRNA表达水平低于对照组;流产组蜕膜绒毛组织中NKG2D、MICA和IL-8蛋白表达低于对照组,差异均有统计学意义.MICA存在于绒毛组织合体滋养层细胞、细胞滋养层细胞及蜕膜组织基质细胞中.NKG2D、MICA与IL-8 mRNA呈正相关(r=0.71、0.74,P<0.05);NKG2D、MICA与IL-8蛋白呈正相关(r=0.76、0.77,P<0.05).结论 ESA患者蜕膜绒毛组织中NKG2D、MICA和IL-8 mRNA和蛋白表达水平低,这可能是导致滋养细胞侵袭性降低并发生ESA的重要原因.

  3. The role of serum IL-8, IL-1β and plasma TNF-α level changes in the development of COPD

    International Nuclear Information System (INIS)

    Objective: To investigate the role of changes of serum IL-8, I-1β and plasma TNF-α levels as well as the contents of these cytokines in induced sputum in the development of COPD. Methods: Blood levels and induced sputum contents of these cytokines (IL-8, IL-1β, TNF-α) were measured with RIA in 88 patients with COPD both during exacerbation and remission as well as in 96 controls. Forced expiratory volume at 1 second (FEV 1.0) were examined in patients with COPD during acute exacerbation. Results: Both the blood levels and induced sputum contents of these cytokines in the controls were significantly lower than those in patients with COPD, either during exacerbation or remission. The levels of cytokines were negatively correlated with the FEV 1.0/ forced vital capacity in patients with COPD during exacerbation. Conclusion: The cytokines IL-8, IL-1β and TNF-α played important role in the development and exacerbation of COPD and were closely related to systemic inflammatory reaction. (authors)

  4. The Effect of 8 Weeks Endurance Training on Serum Levels of IL-10 and IL-8, and White Blood Cell Count in Women with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Abdolreza Kazemi

    2016-09-01

    Full Text Available Background & Objective: The regular exercise training is known as a preventive and adjuvant therapy in inflammatory diseases such as cancer. The aim of this study was to determine the effect of the aerobic training on IL-10 and IL-8 levels and the count of white blood cells (WBC in women with breast cancer. Material & Methods: The statistical society of the present study included Kerman women with breast cancer. Forty patients with breast cancer were randomly divided into two groups: exercise (n = 20 and control (n = 20. The exercise group performed the endurance training for 8 weeks with the intensity between 40 to 55 percent of the target heart rate. Twenty four hours before the first session and 48 hours after the last session of the exercise protocol, blood samples were taken from both groups and then IL-10 and IL-8 levels in serum were measured by ELISA via a Boster kit. Results: The results of the present study showed that 8 weeks of the endurance exercise training did not significantly increase the IL-10 (P=0.113 serum level, but increased the WBC count (p=0.019 and decreased the serum level of IL-8 (p=0.03 significantly. Conclusion: According to the results of the present study, regular endurance training via decreasing the inflammatory factors can be considered as an effective factor along with other therapies in improving breast cancer.

  5. Generation of IL-8 and IL-9 Producing CD4+ T Cells Is Affected by Th17 Polarizing Conditions and AHR Ligands

    Directory of Open Access Journals (Sweden)

    Michaela Gasch

    2014-01-01

    Full Text Available The T helper cell subsets Th1, Th2, Th17, and Treg play an important role in immune cell homeostasis, in host defense, and in immunological disorders. Recently, much attention has been paid to Th17 cells which seem to play an important role in the early phase of the adoptive immune response and autoimmune disease. When generating Th17 cells under in vitro conditions the amount of IL-17A producing cells hardly exceeds 20% while the nature of the remaining T cells is poorly characterized. As engagement of the aryl hydrocarbon receptor (AHR has also been postulated to modulate the differentiation of T helper cells into Th17 cells with regard to the IL-17A expression we ask how far do Th17 polarizing conditions in combination with ligand induced AHR activation have an effect on the production of other T helper cell cytokines. We found that a high proportion of T helper cells cultured under Th17 polarizing conditions are IL-8 and IL-9 single producing cells and that AHR activation results in an upregulation of IL-8 and a downregulation of IL-9 production. Thus, we have identified IL-8 and IL-9 producing T helper cells which are subject to regulation by the engagement of the AHR.

  6. Learning Cascading

    CERN Document Server

    Covert, Michael

    2015-01-01

    This book is intended for software developers, system architects and analysts, big data project managers, and data scientists who wish to deploy big data solutions using the Cascading framework. You must have a basic understanding of the big data paradigm and should be familiar with Java development techniques.

  7. A genome-wide small interfering RNA (siRNA) screen reveals nuclear factor-κB (NF-κB)-independent regulators of NOD2-induced interleukin-8 (IL-8) secretion.

    Science.gov (United States)

    Warner, Neil; Burberry, Aaron; Pliakas, Maria; McDonald, Christine; Núñez, Gabriel

    2014-10-10

    NOD2 encodes an intracellular multidomain pattern recognition receptor that is the strongest known genetic risk factor in the pathogenesis of Crohn disease (CD), a chronic relapsing inflammatory disorder of the intestinal tract. NOD2 functions as a sensor for bacterial cell wall components and activates proinflammatory and antimicrobial signaling pathways. Here, using a genome-wide small interfering RNA (siRNA) screen, we identify numerous genes that regulate secretion of the proinflammatory cytokine IL-8 in response to NOD2 activation. Moreover, many of the identified IL-8 regulators are linked by protein-protein interactions, revealing subnetworks of highly connected IL-8 regulators implicated in processes such as vesicle formation, mRNA stability, and protein ubiquitination and trafficking. A TNFα counterscreen to induce IL-8 secretion in an NOD2-independent manner reveals that the majority of the identified regulators affect IL-8 secretion irrespective of the initiating stimuli. Using immortalized macrophages, we validate the ubiquitin protease, USP8, and the endosomal sorting protein, VPS28, as negative regulators of NOD2-induced cytokine secretion. Interestingly, several genes that affect NOD2-induced IL-8 secretion are present in loci associated with CD risk by genome-wide association studies, supporting a role for the NOD2/IL-8 pathway, and not just NOD2, in the pathogenesis of CD. Overall, this screen provides a valuable resource in the advancement of our understanding of the genes that regulate the secretion of IL-8. PMID:25170077

  8. A Genome-wide Small Interfering RNA (siRNA) Screen Reveals Nuclear Factor-κB (NF-κB)-independent Regulators of NOD2-induced Interleukin-8 (IL-8) Secretion*

    Science.gov (United States)

    Warner, Neil; Burberry, Aaron; Pliakas, Maria; McDonald, Christine; Núñez, Gabriel

    2014-01-01

    NOD2 encodes an intracellular multidomain pattern recognition receptor that is the strongest known genetic risk factor in the pathogenesis of Crohn disease (CD), a chronic relapsing inflammatory disorder of the intestinal tract. NOD2 functions as a sensor for bacterial cell wall components and activates proinflammatory and antimicrobial signaling pathways. Here, using a genome-wide small interfering RNA (siRNA) screen, we identify numerous genes that regulate secretion of the proinflammatory cytokine IL-8 in response to NOD2 activation. Moreover, many of the identified IL-8 regulators are linked by protein-protein interactions, revealing subnetworks of highly connected IL-8 regulators implicated in processes such as vesicle formation, mRNA stability, and protein ubiquitination and trafficking. A TNFα counterscreen to induce IL-8 secretion in an NOD2-independent manner reveals that the majority of the identified regulators affect IL-8 secretion irrespective of the initiating stimuli. Using immortalized macrophages, we validate the ubiquitin protease, USP8, and the endosomal sorting protein, VPS28, as negative regulators of NOD2-induced cytokine secretion. Interestingly, several genes that affect NOD2-induced IL-8 secretion are present in loci associated with CD risk by genome-wide association studies, supporting a role for the NOD2/IL-8 pathway, and not just NOD2, in the pathogenesis of CD. Overall, this screen provides a valuable resource in the advancement of our understanding of the genes that regulate the secretion of IL-8. PMID:25170077

  9. Evaluation of serum enzymes polypeptide, chemokine levels and peripheral blood immune cells contents in children with bronchial asthma

    Institute of Scientific and Technical Information of China (English)

    Zhong-Yong Xie; Wei-Ming Chen; Wei-Zhong Zhang; Shang-Hong Tang

    2015-01-01

    Objective:To evaluate serum enzymes polypeptide, chemokine levels and peripheral blood immune cells contents of children with bronchial asthma.Methods:150 bronchial asthma children were enrolled as observation group, 120 healthy children received physical examination in our hospital over the same period were enrolled as control group. Then serum enzymes polypeptide, chemokine levels and peripheral blood immune cells contents were detected.Results:(1) Enzyme polypeptide: serum Cat K, MMP1, MMP2, MMP9 contents of observation group were significant higher than those of the control group; but TIMP1 content was lower than that of control group; (2)Chemokine: serum Eotaxin, MCP-1, MCP-4, MDC and IL-8 contents of observation group were higher than those of the control group; (3) Immune cell: Th1 cell, CD4+CD25+T cell and CD8+CD28+T cell contents of observation group were significant lower than those of the control; but Th2 cells and Th17 cells were higher than those of control group.Conclusions:Serum enzymes polypeptide and chemokine levels of children with bronchial asthma abnormally increase with presence of peripheral blood T cell subsets contents disorder, which is correlated with airway remodeling and inflammatory cell infiltration process.

  10. 伴有牙周炎的IgA肾病患者牙周治疗前后血清TNF-α与IL-8变化分析%Changes in levels of serum TNF-α and IL-8 before and after periodontal therapy for patients of IgA nephropathy with periodontitis

    Institute of Scientific and Technical Information of China (English)

    许志鹏; 宋勇; 孙燕

    2015-01-01

    Objective To examine the levels of serum tumor necrosis factor-α(TNF-α) and interleukin-8 (IL-8) for IgA nephropathy patients with periodontitis before and after periodontal therapy. Methods Fifty pa-tients of IgA nephropathy with chronic periodontitis (study group) and 30 healthy individuals (control group) were in-cluded in this study. The study group was treated by ultrasonic and VECTOR periodontal therapy apparatus, whereas the control group received no special treatment. We measured the periodontal indexes, and serum TNF-αand IL-8 lev-els by enzyme-linked immunosorbent assay (ELISA) at the visit of doctor in the control group as well as before treat-ment and 4 weeks after treatment in the study group. Results After periodontal therapy, the periodontal status was significantly improved, with the levels of periodontal indexes and serum TNF-α and IL-8 significantly decreased. Compared with the control group, the periodontal indexes and the serum TNF-αand IL-8 were still significantly higher. Conclusion Periodontal treatment can not only effectively improve the periodontal lesions and promote the recovery of periodontitis, but also reduce the levels of serum TNF-αand IL-8 and benefit the treatment for IgA nephropathy.%目的:观察伴有慢性牙周炎的IgA肾病患者牙周治疗前后血清肿瘤坏死因子-α(TNF-α)和白细胞介素-8(IL-8)变化。方法选取伴有慢性牙周炎的IgA肾病患者50例(治疗组)和健康者30例(对照组)。对照组不予特殊处理,治疗组采用超声洁牙和VECTOR牙周治疗仪进行牙周治疗,对照组于初诊时,治疗组于治疗前及治疗后4周,分别检测两组受试者的牙周指数和血清TNF-α与IL-8的浓度。血清中TNF-α与IL-8的浓度采用酶联免疫吸附法测定。结果治疗组患者经过牙周治疗后,牙周状况明显好转,血清TNF-α与IL-8浓度与治疗前比较均明显降低,差异均有统计学意义(P<0.05),但是牙周指数、TNF-α和IL-8

  11. Dynamic changes of IL-2, sIL-2R, IL-6 and IL-8 in children with mycoplasma pneumonia and their clinical significance%肺炎支原体肺炎IL-2、sIL-2R、IL-6、IL-8检测

    Institute of Scientific and Technical Information of China (English)

    刘文彬; 赵文利; 汤雪琴; 袁丽

    2012-01-01

    目的 探讨肺炎支原体肺炎(MPP)急性期和恢复期免疫功能动态变化及临床意义.方法 检测IL-2、sIL-2R、IL-6、IL-8均采用ELISA双抗体夹心法.结果 与对照组比较,MPP患儿急性期sIL-2R、IL-6,IL-8值均明显升高(P<0.01),IL-2值均明显下降(P<0.01),与急性期比较,MPP患儿恢复期IL-2值均明显升高(P<0.01),而sIL-2R、IL-6、IL-8值均明显下降(P<0.01);与对照组比较,MPP患儿恢复期IL-2、sIL-2R、IL-6、IL-8均无明显改变(P>0.05).结论 MPP患儿存在细胞免疫功能低下及紊乱,IL-2、sIL-2R、IL-6及IL-8值恢复较快,检测MPP患儿免疫功能,特别是IL-2、sIL-2R、IL-6和IL-8水平对疗效及预后的判定有重要价值.%Objective To observe the dynamic changes of IL-2, sIL-2R, IL-6 and IL-8 in children with mycoplasma pneumonia( MPP) and to study their clinical significance. Methods The serum levels of IL-2, sIL-2R, IL-6 and IL-8 in 40 children with MPP during the acute stage and convalescent stage were examined with double-antibody sandwich enzyme-linked immu-nosobent assay, and the results were compared with those in 30 normal children. Results The levels of slL-2R, IL-6 and IL-8 were higher and IL-2 was lower during acute stage than those in the normal subjects (P <0. 01). Compared those during the convalescent stage, the level of IL-2 was higher and sIL-2R, IL-6 and IL-8 were lower (P <0. 01) during the acute stage. There were not any significant differences of the levels of these four substances between the normal children and MPP children during the convalescent stage. Conclusion The cellular immune function of children with MPP is impaired and the changes of IL-2, sIL-2R, IL-6 and IL-8 can be used to evaluate the curative effects and prognosis of MPP in children.

  12. CA153、IL-6及IL-8与乳腺癌骨转移相关性探讨%Study on the correlation between CA153, IL-6, IL-8 levels and bone metastasis in patients with breast cancer

    Institute of Scientific and Technical Information of China (English)

    杨士军; 谭维琴; 鲍艳梅

    2011-01-01

    目的 探讨糖类抗原153(CA153)及细胞因子[白细胞介素6(IL-6)、白细胞介素8(IL-8)]与乳腺癌骨转移的关系.方法 对103例乳腺癌根治手术后患者行单光子发射型(SPECT)骨显像,采用放射免疫法检测血清CA153,放射免疫分析法检测IL-6、IL-8水平,与健康对照组(36例)进行对比分析.结果 骨转移组患者血清CA153、IL-6、IL-8水平明显升高,与无骨转移组及健康对照组比较差异均有统计学意义(P0.05).结论 CA153对于预测乳腺癌骨转移、筛选行全身骨显像患者具有重要意义;IL-6、IL-8参与乳腺癌骨转移的发生和发展过程,检测IL-6、IL-8对于乳腺癌骨转移的病理研究和预防、治疗可能具有重要价值.%Objective To investigate the corelation of CA153,IL-6,IL-8 and breast cancer bone metastasis. Methods 103 breast cancer patients after radical surgery were scanned by single photon emission computer tomography(SPECT). Immunoradiometric assay(IRMA) method was used to assay the serum.level of CA153,and radioimmunoassay(RIA) method was used to assay serum level of IL-6,IL-8;At the same time,the result was analyzed against the control group of 36 normal people. Results In breast cancer patients group with bone metastasis, the serum level of CA153, IL-6, IL-8 were significantly higher than normal people(P<0.05) ,while the serum level of CA153,IL-6 and IL-8 in cancer patients group without bone metastasis and in control group were not statistically significant different(P>0.05). Conclusion CA153 has great significance in predicting breast cancer bone metastasis and screening whole body bone imaging;IL-6, IL-8 is engaging in the occurrence and development of bone metastasis, assaying the serum levels of IL-6,IL-8 are of great value to pathology research,prevention and treatment of breast cancer bone metastasis.

  13. Expression levels of novel cytokine IL-32 in periodontitis and its role in the suppression of IL-8 production by human gingival fibroblasts stimulated with Porphyromonas gingivalis

    Directory of Open Access Journals (Sweden)

    Kazuhisa Ouhara

    2012-03-01

    Full Text Available Background:IL-32 was recently found to be elevated in the tissue of rheumatoid arthritis and inflammatory bowel disease. Periodontitis is a chronic inflammatory disease caused by polymicrobial infections that result in soft tissue destruction and alveolar bone loss. Although IL-32 is also thought to be associated with periodontal disease, its expression and possible role in periodontal tissue remain unclear. Therefore, this study investigated the expression patterns of IL-32 in healthy and periodontally diseased gingival tissue. The expression of IL-32 in cultured human gingival fibroblasts (HGF as well as effects of autocrine IL-32 on IL-8 production from HGF were also examined.Methods:Periodontal tissue was collected from both healthy volunteers and periodontitis patients, and immunofluorescent staining was performed in order to determine the production of IL-32. Using real-time PCR and ELISA, mRNA expression and protein production of IL-32 in HGF, stimulated by Porphyromonas gingivalis (Pg, were also investigated.Results:Contrary to our expectation, the production of IL-32 in the periodontitis patients was significantly lower than in the healthy volunteers. According to immunofluorescent microscopy, positive staining for IL-32 was detected in prickle and basal cell layers in the epithelium as well as fibroblastic cells in connective tissue. Addition of fixed Pg in vitro was found to suppress the otherwise constitutive expression of IL-32 mRNA and protein in HGF. However, recombinant IL-32 in vitro inhibited the expression of IL-8 mRNA by HGF stimulated with Pg. Interestingly, anti-IL-32 neutralizing antibody upregulated the IL-8 mRNA expression in non-stimulated HGF, indicating that constitutive expression of IL-32 in HGF suppressed IL-8 mRNA expression in the absence of bacterial stimulation.Conclusion:These results indicate that IL-32 is constitutively produced by HGF which can be suppressed by Pg and may play a role in the downregulation

  14. Evaluation of the role of leptin, interleukin-8 (Il-8) and nitric oxide (No) in children with insulin dependent diabetes mellitus (type 1)

    International Nuclear Information System (INIS)

    The autoimmune nature of insulin dependent diabetes mellitus (IDDM), type 1, is well established. The documentation of altered Th 1/Th 2 balance and the finding of antibodies in the circulation directed against the b-cells can indicate the role of the immune system. The stimulating effect of insulin on leptin expression is well identified. The aim of this study is to investigate the profile and the relationships between leptin, interleukin-8 (IL-8) and nitric oxide (NO) and to reveal their possible role in the development and progression of IDDM. Serum leptin was evaluated using radioimmunoassay (RIA), serum concentration of IL-8 was assayed by enzyme linked immunosorbent assay (ELISA), while serum nitrite level (end product of NO) was determined by Griess reaction. The study was carried out on twenty IDDM children who compared with other twenty healthy non-diabetic ones with the same age and sex. The data revealed that children with IDDM established high weight-for-age (W/A)Z (P < 0.001) , high weight-for-height (W/H)Z (P < 0.05) and high glycated hemoglobin (HbA1c% ) (P < 0.0001). Both diabetic boys and girls showed higher serum leptin levels (7.48 ± 1.86 ng/ml) than the control group (5.92 ± 1.39 ng/ml). Leptin levels were higher in diabetic girls (8.46 ± 2.29 ng/ml) than diabetic boys (6.68 ± 0.91 ng/ml). Significant high level of serum IL-8 concentration (23 ± 11.92 pg/ml) was detected in IDDM children versus the control group (5.69 ± 1.67 pg/ml). On the other hand, serum nitrite values showed significant reduction in the IDDM children (430.78 ± 155.14 Μmol/l) compared to the control group (610.08 ± 192.82 Μmol/l). Correlation analysis showed positive correlation between leptin with age, (W/H)Z and fasting glucose level, furthermore, a positive correlation was established between IL-8 with (W/H)Z, hinting the adipose tissue as a site of its production and no association between NO and other relevant variables was detected. It could be concluded that

  15. Cytokines and Chemokines as Biomarkers of Community-Acquired Bacterial Infection

    Directory of Open Access Journals (Sweden)

    Michal Holub

    2013-01-01

    Full Text Available Routinely used biomarkers of bacterial etiology of infection, such as C-reactive protein and procalcitonin, have limited usefulness for evaluation of infections since their expression is enhanced by a number of different conditions. Therefore, several inflammatory cytokines and chemokines were analyzed with sera from patients hospitalized for moderate bacterial and viral infectious diseases. In total, 57 subjects were enrolled: 21 patients with community-acquired bacterial infections, 26 patients with viral infections, and 10 healthy subjects (control cohorts. The laboratory analyses were performed using Luminex technology, and the following molecules were examined: IL-1Ra, IL-2, IL-4, IL-6, IL-8, TNF-α, INF-γ, MIP-1β, and MCP-1. Bacterial etiology of infection was associated with significantly (P<0.001 elevated serum concentrations of IL-1Ra, IL-2, IL-6, and TNF-α in comparison to levels observed in the sera of patients with viral infections. In the patients with bacterial infections, IL-1Ra and IL-8 demonstrated positive correlation with C-reactive protein, whereas, IL-1Ra, TNF-α, and MCP-1 correlated with procalcitonin. Furthermore, elevated levels of IL-1Ra, IL-6, and TNF-α decreased within 3 days of antibiotic therapy to levels observed in control subjects. The results show IL-1Ra as a potential useful biomarker of community-acquired bacterial infection.

  16. Chemokine-Releasing Nanoparticles for Manipulation of the Lymph Node Microenvironment

    Directory of Open Access Journals (Sweden)

    Taissia G. Popova

    2015-03-01

    Full Text Available Chemokines (CKs secreted by the host cells into surrounding tissue establish concentration gradients directing the migration of leukocytes. We propose an in vivo CK gradient remodeling approach based on sustained release of CKs by the crosslinked poly(N-isopropylacrylamide hydrogel open meshwork nano-particles (NPs containing internal crosslinked dye affinity baits for a reversible CK binding and release. The sustained release is based on a new principle of affinity off-rate tuning. The NPs with Cibacron Blue F3G-A and Reactive Blue-4 baits demonstrated a low-micromolar affinity binding to IL-8, MIP-2, and MCP-1 with a half-life of several hours at 37 °C. The capacity of NPs loaded with IL-8 and MIP-1α to increase neutrophil recruitment to lymph nodes (LNs was tested in mice after footpad injection. Fluorescently-labeled NPs used as tracers indicated the delivery into the sub-capsular compartment of draining LNs. The animals administered the CK-loaded NPs demonstrated a widening of the sub-capsular space and a strong LN influx of leukocytes, while mice injected with control NPs without CKs or bolus doses of soluble CKs alone showed only a marginal neutrophil response. This technology provides a new means to therapeutically direct or restore immune cell traffic, and can also be employed for simultaneous therapy delivery.

  17. Clinical Significance of Determination of Changes of Serum of TNF-α, IL-6, IL-8,IL-10 Levels After Treatment in Patients with Condyloma Acuminatum%尖锐湿疣患者治疗前后血清TNF-α、IL-6、IL-8、IL-10检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    王亚平

    2007-01-01

    目的:探讨了尖锐湿疣患者治疗前后血清TNF-α、IL-6、IL-8、IL-10水平变化及意义.方法:应用RIA和ELISA对40例尖锐湿疣患者进行了血清TNF-α、IL-6、IL-8、IL-10水平检测并与35名正常健康人作比较.结果:在治疗前尖锐湿疣患者血清IL-6及IL-8低于正常对照组.TNF-α、IL-10水平均非常显著地高于正常对照组(P<0.01),经治疗3个月后与正常对照组比较仍有显著性差异(P<0.05).结论:检测尖锐湿疣患者血清TNF-α、IL-6、IL-8、IL-10水平的变化对疾病的治疗、预后观察有重要的临床价值.

  18. Clinical Significance of Measurement of Changes of Serum TNF-α, IL-6 and IL-8 Centent After Treatment in Patients with Pregnancy Induced Hypertension (PIH)%妊高征患者治疗前后血清TNF-α、IL-6和IL-8检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    王桂英

    2008-01-01

    目的:探讨了妊高征患者治疗前后血清TNF-α、IL-6和IL-8水平的变化及意义.方法:采用放射免疫分析对36例妊高征患者进行了血清TNF-α、IL-6和IL-8水平检测并与35名正常孕妇作比较.结果:在治疗前血清TNF-α、IL-6和IL-8水平非常显著地高于正常孕妇组(P0.05).结论:炎性细胞因子TNF-α、IL-6和IL-8在妊高征的发病机理中具有重要的作用,有一定的临床价值.

  19. The expression and significance of epithelial neutrophil ENA-78、IL-8 in endometriosis%子宫内膜异位症中趋化性细胞因子ENA-78、IL-8的表达及意义

    Institute of Scientific and Technical Information of China (English)

    姚赛君

    2008-01-01

    目的:探讨趋化性细胞因子ENA-78、IL-8在子宫内膜异位症(EM)发病机制中的作用.方法:应用酶联免疫吸附法测定50例EM患者及20例非EM患者(对照组)腹腔液中ENA-78和IL-8水平.结果:EM组患者腹腔液ENA-78、IL-8的水平 (326.25±231.35pg/ml、3.58±1.98 ng/ml)均显著高于对照组 (123.85±61.42pg/ml、1.25±0.78ng/ml)(P0.05).结论:EM患者腹腔液中ENA-78、IL-8水平增高,与期别相关,可能为子宫内膜异位症的发病因素之一.

  20. The changes and clinical significance of Sp- selectin and IL- 8 in patients with colorectal carcinoma%结直肠癌患者血清sP-selectin和IL-8水平的变化及其临床意义

    Institute of Scientific and Technical Information of China (English)

    孟明; 陈冬志; 王锡明

    2003-01-01

    目的:探讨结直肠癌患者手术前后血清中可溶性 sP- selectin和 IL- 8含量的变化及其临床意义.方法:用 ELISA法和 RIA法分别测定结直肠癌患者手术前、手术后及复发病人血清 sP- selectin和 IL- 8的含量,并与对照组进行比较.结果:结直肠癌患者血清 sP- selectin和 IL- 8的含量明显高于正常人( P<0.01),术后 3个月下降至接近正常人水平,而 复发患者则再次升高( P<0.01).结论:血清 sP- selectin和 IL- 8的含量与结直肠癌的发展及预后密切相关.

  1. Neutronic exposure and early increase of IL-6, IL-8 and G-csf seric levels in non human primates; Elevation precoce des concentrations seriques d`IL-6, d`IL-8 et de G-CSF apres exposition neutronique

    Energy Technology Data Exchange (ETDEWEB)

    Van Uye, A.; Agay, D.; Edgard, L.; Cruz, C.; Mestries, J.C. [Centre de Recherches du Service de Sante des Armees, La Tronche, 38 - Grenoble (France)

    1997-12-31

    The aim of the work was to study some of the early events that trigger radiation-induced inflammatory response. Blood kinetic profiles of IL-6, IL-8 and G-CSF were monitored in male adult baboons (Papio sp.) within the first 24 hours following the exposure to a 6 Gy mixed neutron-gamma field. (authors)

  2. Reactive oxygen species and chemokines:Are they elevated in the esophageal mucosa of children with gastroesophageal reflux disease?

    Institute of Scientific and Technical Information of China (English)

    Engin Tutar; Deniz Ertem; Goksenin Unluguzel; Sevda Tanrikulu; Goncagul Haklar; Cigdem Celikel; Evin Ademoglu; Ender Pehlivanoglu

    2008-01-01

    AIM:To determine the role of inflammatory cytokines and reactive oxygen species (ROS) in childhood reflux esophagitis.METHODS:A total of 59 subjects who had complaints suggesting GERD underwent esophagogastroduoden oscopy.Endoscopic and histopathologic diagnosis of reflux esophagitis was established by Savary-Miller and Vandenplas grading systems,respectively.Esophageal biopsy specimens were taken from the esophagus 20% proximal above the esophagogastric junction for conventional histopathological examination and the measurements of ROS and cytokine levels.ROS were measured by chemiluminescence,whereas IL-8 and MCP-1 levels were determined with quantitative immunometric ELISA on esophageal tissue.Esophageal tissue ROS,IL-8 and MCP-1 levels were compared among groups with and without endoscopic/histopathologic esophagitis.RESULTS:Of 59 patients 28 (47.5%) had normal esophagus whereas 31 (52.5%) had endoscopic esophagitis.In histopathological evaluation,almost 73% of the cases had mild and 6.8% had moderate degree of esophagitis.When ROS and chemokine levels were compared among groups with and without endoscopic esophagitis,statistical difference could not be found between patients with and without esophagitis.Although the levels of ROS,IL-8 and ICP-1 were found to be higher in the group with histopathological reflux esophagitis,this difference was not statistically significant.CONCLUSION:These results suggest that the grade of esophagitis is usually mild or moderate during childhood and factors apart from ROS,IL-8 and MCP-1 may be involved in the pathogenesis of reflux esophagitis in children.

  3. Clinical significance on the changes of serum IL-6,IL-8 and IL-10 levels in children with H.pylori infection%幽门螺杆菌感染患儿血清 IL-6、IL-8、IL-10水平变化

    Institute of Scientific and Technical Information of China (English)

    陈一; 阎晓莉; 李华; 拜康利

    2003-01-01

    为探讨各种细胞因子在幽门螺杆菌相关性胃肠粘膜病中的作用机理及意义,采用 ELISA法,检测 35例幽门螺杆菌阳性患儿血清 IL-6、 IL-8、 IL-10水平,并与幽门螺杆菌阴性组 31例作对照.结果显示两组间 IL-6、 IL-8分布水平差异有极显著性( P<0.001);两组间 IL-10分布水平差异有显著性( P<0.05).幽门螺杆菌阳性组与阴性组 IL-6平均秩和之差为 16.38,均数分别为 108.46pg/ml及 51.32pg/ml; IL-8平均秩和之差为 34,均数分别为 163.09pg/ml及 92.36pg/ml; IL-10平均秩和之差为- 3.32,均数分别为 12.56pg/ml及 15.88pg/ml.幽门螺杆菌阳性组血清 IL-6与 IL-8间呈正相关( r=0.349, P<0.001); IL-10与 IL-6、 IL-8间无明显相关性.提示细胞因子 IL-6、 IL-8、 IL-10均参与了幽门螺杆菌感染后的致病过程;幽门螺杆菌感染胃肠粘膜产生的炎症反应损伤与 IL-6、 IL-8的过量产生有关,血清 IL-10对炎症有抑制作用,从而为临床诊治幽门螺杆菌相关性疾病提供理论依据.

  4. Changes and significance of IL-6, IL-8 and TNF-α in serum of breast cancer patients before and after chemotherapy%化疗前后乳腺癌患者血清中IL-6、IL-8及TNF-α的变化及意义

    Institute of Scientific and Technical Information of China (English)

    杨明德; 李冬梅; 于慧玲

    2015-01-01

    目的:探讨化疗前后乳腺癌患者血清中IL-6、IL-8及TNF-α的变化及意义.方法:选择住院手术乳腺癌术后1个月、化疗1个疗程(21天)患者50例,化疗前、后均静脉采血,同期选取体检健康女性30例作为对照组亦静脉采血,均留取血清待测.采用ELISA酶联免疫法检测IL-6、IL-8及TNF-α的蛋白水平,采用流式细胞免疫学法检测IL-6、IL-8及TNF-α的细胞阳性百分率.结果:与对照组比较,化疗前乳腺癌组患者血清中IL-6、IL-8、TNF-α的蛋白水平及细胞阳性百分率均升高,差异有统计学意义(P<0.01);化疗后患者血清中IL-6、IL-8、TNF-α的蛋白水平及细胞阳性百分率均略升高,差异无统计学意义(P>0.05);化疗前乳腺癌组患者血清中IL-6、IL-8、TNF-α的蛋白水平及细胞阳性百分率明显高于化疗后患者,差异有统计学意义(P<0.01).结论:化疗能够通过降低乳腺癌患者血清中IL-6、IL-8、TNF-α的水平抑制肿瘤的浸润和转移,这为乳腺癌的临床治疗提供新的靶点.

  5. Interaction of chemokines with their receptors--from initial chemokine binding to receptor activating steps

    DEFF Research Database (Denmark)

    Thiele, Stefanie; Rosenkilde, Mette Marie

    2014-01-01

    interactions possibly occur, resulting in a multi-step process, as recently proposed for other 7TM receptors. Overall, the N-terminus of chemokine receptors is pivotal for binding of all chemokines. During receptor activation, differences between the two major chemokine subgroups occur, as CC-chemokines mainly......The human chemokine system comprises 19 seven-transmembrane helix (7TM) receptors and 45 endogenous chemokines that often interact with each other in a promiscuous manner. Due to the chemokine system's primary function in leukocyte migration, it has a central role in immune homeostasis...... and surveillance. Chemokines are a group of 8-12 kDa large peptides with a secondary structure consisting of a flexible N-terminus and a core-domain usually stabilized by two conserved disulfide bridges. They mainly interact with the extracellular domains of their cognate 7TM receptors. Affinityand activity...

  6. Clinical Study of Serum IL-13,IL-8,TNF-α,TIgE Level in Children with Bronchiolitis%婴幼儿毛细支气管炎患者血清IL-13、IL-8、TNF-α、TIgE水平的临床研究

    Institute of Scientific and Technical Information of China (English)

    王峻; 李峰; 王丽

    2014-01-01

    目的:探讨婴幼儿毛细支气管炎患者血清白细胞介素13(IL-13)、白细胞介素8(IL-8)、肿瘤坏死因子(TNF-α)、TIgE的水平及临床意义。方法:选取36例急性期毛细支气管炎患儿(其中轻症组20例,重症组16例)、30例普通肺炎患儿以及30例同期健康查体儿,采用酶联免疫吸附法ELISA法检测三组的血清IL-13、IL-8、TNF-α、TIgE水平。结果:两组肺炎患儿血清IL-13、IL-8、TNF-α水平均显著高于正常对照组(P<0.05);毛支炎组血清IL-13、IL-8、TNF-α、TIgE均高于普通肺炎组(P<0.05);毛支炎重症组的TNF-α高于轻症组(P<0.05)。结论:IL-13、IL-8、TNF-α参与毛细支气管炎的发病过程,TNF-α水平与毛支炎病情相关,且毛支炎患儿血清TIgE高于正常对照组。%Objective:To study the clinical significance on serum level of interleukin 13(IL-13),interleukin 8(IL-8),tumor necrosis factor(TNF-α),TIgE in infants with bronchiolitis. Method:36 cases of infantile with bronchiolitis(20 cases of the mild group and 16 cases of the severe group),and 30 cases of ordinary pneumonia,with 30 healthy infants were checked for the IL-13,IL-8,TNF-αand TIgE level with ELISA method.Result:The IL-13,IL-8, TNF-αlevel in the two groups of children with bronchiolitis and ordinary pneumonia were significantly higher than that in the normal control group(P<0.05);the IL-13,IL-8,TNF-α,TIgE level in the bronchiolitis group were higher than the ordinary pneumonia group(P<0.05);the level of TNF-αof the bronchiolitis severe group was higher than that in the mild group(P<0.05). Conclusion:IL-13,IL-8,TNF-αlevels play an important role in the process of bronchiolitis, and TNF-αlevel has association with the course and conditions of the disease;the serum level of TIgE is higher in the bronchiolitis infants than that of other control group.

  7. Clinical Significance of Determination of Changes of Serum CA153, IL-6, IL-8 and TNF-α Levels in Patients with Breast Cancer%乳腺癌患者手术治疗前后血清CA153、IL-6、IL-8和TNF-α测定的临床意义

    Institute of Scientific and Technical Information of China (English)

    王昭昕

    2006-01-01

    目的:探讨了乳腺癌患者手术治疗前后血清CA153、IL-6、IL-8和TNF-α含量的变化.方法:分别应用放射免疫分析和酶联免疫分析对38例乳腺癌患者进行了手术治疗前后血清CA153、IL-6、IL-8和TNF-α含量检测,并与30名正常健康人作比较.结果:乳腺癌患者手术前血清CA153、IL-6、IL-8和TNF-α水平非常显著地高于正常人组(P<0.01),3个月后已降至正常人组水平(P>0.05).手术切除1年后复发者血清IL-6、IL-8和TNF-α水平持续异常,未复发者基本接近正常.结论:检测血清CA153、IL-8、IL-6和TNF-α的水平与乳腺癌患者的病情和预后密切相关,具有一定的临床实用价值.

  8. The Expression of IL-8 mRNA,TSP-1 mRNA and Their Clinicopathologic Value in the Breast Cancer%乳腺癌IL-8mRNA和TSP-1mRNA检测及临床病理意义

    Institute of Scientific and Technical Information of China (English)

    李树根; 尹新民; 李艳春

    2004-01-01

    目的研究乳腺癌和小叶增生组织中IL-8mRNA和TSP-1mRNA表达水平及临床病理意义.方法 58例乳腺癌和15例小叶增生病例标本经10%福尔马林固定后常规制作石蜡包埋切片.IL-8mRNA、TSP-1mRNA染色方法为原位杂交法.结果乳腺癌IL-8mRNA阳性率明显高于小叶增生(56.9% vs 13.3%,P<0.01),但TSP-1mRNA则相反(48.3% vs 86.7%,P<0.01),且IL-8mRNA阳性和TSP-1mRNA阴性表达小叶增生均为相同病例;组织学分级I级和淋巴结未转移病例IL-8mRNA和TSP-1mRNA表达可能是反映乳腺癌生物学行为和预后的重要标记物.结论联合两者检测乳腺良性病变中的表达对预防和早期发现乳腺癌可能有重要临床意义.

  9. Chemokine Systems Link Obesity to Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Tsuguhito Ota

    2013-06-01

    Full Text Available Obesity is a state of chronic low-grade systemic inflammation. This chronic inflammation is deeply involved in insulin resistance, which is the underlying condition of type 2 diabetes and metabolic syndrome. A significant advance in our understanding of obesity-associated inflammation and insulin resistance has been recognition of the critical role of adipose tissue macrophages (ATMs. Chemokines are small proteins that direct the trafficking of immune cells to sites of inflammation. In addition, chemokines activate the production and secretion of inflammatory cytokines through specific G protein-coupled receptors. ATM accumulation through C-C motif chemokine receptor 2 and its ligand monocyte chemoattractant protein-1 is considered pivotal in the development of insulin resistance. However, chemokine systems appear to exhibit a high degree of functional redundancy. Currently, more than 50 chemokines and 18 chemokine receptors exhibiting various physiological and pathological properties have been discovered. Therefore, additional, unidentified chemokine/chemokine receptor pathways that may play significant roles in ATM recruitment and insulin sensitivity remain to be fully identified. This review focuses on some of the latest findings on chemokine systems linking obesity to inflammation and subsequent development of insulin resistance.

  10. Soluble M3 proteins of murine gammaherpesviruses 68 and 72 expressed in Escherichia coli: analysis of chemokine-binding properties.

    Science.gov (United States)

    Matúšková, R; Pančík, P; Štibrániová, I; Belvončíková, P; Režuchová, I; Kúdelová, M

    2015-12-01

    M3 protein of murine gammaherpesvirus 68 (MHV-68) was identified as a viral chemokine-binding protein 3 (vCKBP-3) capable to bind a broad spectrum of chemokines and their receptors. During both acute and latent infection MHV-68 M3 protein provides a selective advantage for the virus by inhibiting the antiviral and inflammatory response. A unique mutation Asp307Gly was identified in the M3 protein of murine gammaherpesvirus 72 (MHV-72), localized near chemokine-binding domain. Study on chemokine-binding properties of MHV-72 M3 protein purified from medium of infected cells implied reduced binding to some chemokines when compared to MHV-68 M3 protein. It was suggested that the mutation in the M3 protein might be involved in the attenuation of immune response to infection with MHV-72. Recently, Escherichia coli cells were used to prepare native recombinant M3 proteins of murine gammaherpesviruses 68 and 72 (Pančík et al., 2013). In this study, we assessed the chemokine-binding properties of three M3 proteins prepared in E. coli Rosetta-gami 2 (DE3) cells, the full length M3 protein of both MHV-68 and MHV-72 and MHV-68 M3 protein truncated in the signal sequence (the first 24 aa). They all displayed binding activity to human chemokines CCL5 (RANTES), CXCL8 (IL-8), and CCL3 (MIP-1α). The truncated MHV-68 M3 protein had more than twenty times reduced binding activity to CCL5, but only about five and three times reduced binding to CXCL8 and CCL3 when compared to its full length counterpart. Binding of the full length MHV-72 M3 protein to all chemokines was reduced when compared to MHV-68 M3 protein. Its binding to CCL5 and CCL3 was reduced over ten and seven times. However, its binding to CXCL8 was only slightly reduced (64.8 vs 91.8%). These data implied the significance of the signal sequence and also of a single mutation (at aa 307) for efficient M3 protein binding to some chemokines.

  11. Mycobacterium abscessus glycopeptidolipid prevents respiratory epithelial TLR2 signaling as measured by HβD2 gene expression and IL-8 release.

    Directory of Open Access Journals (Sweden)

    Lisa B Davidson

    Full Text Available Mycobacterium abscessus has emerged as an important cause of lung infection, particularly in patients with bronchiectasis. Innate immune responses must be highly effective at preventing infection with M. abscessus because it is a ubiquitous environmental saprophyte and normal hosts are not commonly infected. M. abscessus exists as either a glycopeptidolipid (GPL expressing variant (smooth phenotype in which GPL masks underlying bioactive cell wall lipids, or as a variant lacking GPL which is immunostimulatory and invasive in macrophage infection models. Respiratory epithelium has been increasingly recognized as playing an important role in the innate immune response to pulmonary pathogens. Respiratory epithelial cells express toll-like receptors (TLRs which mediate the innate immune response to pulmonary pathogens. Both interleukin-8 (IL-8 and human β-defensin 2 (HβD2 are expressed by respiratory epithelial cells in response to toll-like receptor 2 (TLR2 receptor stimulation. In this study, we demonstrate that respiratory epithelial cells respond to M. abscessus variants lacking GPL with expression of IL-8 and HβD2. Furthermore, we demonstrate that this interaction is mediated through TLR2. Conversely, M. abscessus expressing GPL does not stimulate expression of IL-8 or HβD2 by respiratory epithelial cells which is consistent with "masking" of underlying bioactive cell wall lipids by GPL. Because GPL-expressing smooth variants are the predominant phenotype existing in the environment, this provides an explanation whereby initial M. abscessus colonization of abnormal lung airways escapes detection by the innate immune system.

  12. RANKL/RANK interaction promotes the growth of cervical cancer cells by strengthening the dialogue between cervical cancer cells and regulation of IL-8 secretion.

    Science.gov (United States)

    Shang, Wen-Qing; Li, Hui; Liu, Li-Bing; Chang, Kai-Kai; Yu, Jia-Jun; Xie, Feng; Li, Ming-Qing; Yu, Jin-Jin

    2015-12-01

    Receptor activator for nuclear factor κB ligand (RANKL) is a member of the tumor necrosis factor (TNF) family. The interaction between RANKL and its receptor RANK plays an important role in the development and function of diverse tissues. However, the expression and role of RANKL in cervical cancer are still unknown. In the present study, we found that RANKL and RANK were highly co-expressed in cervical cancer. HeLa and SiHa cells secreted soluble RANKL (sRANKL), expressed member RANKL (mRANKL) and RANK. Recombinant human RANKL protein had no effect on the viability of HeLa and SiHa cells. Yet, blocking RANKL with an anti-human RANKL neutralizing antibody (α-RANKL) or recombinant human osteoprotegrin (OPG) protein resulted in the downregulation of Ki-67 and B-cell lymphoma 2 (Bcl-2) expression and an increase in Fas and Fas ligand (FasL) expression, as well as a high level of viability and a low level of apoptosis in the HeLa and SiHa cells. In addition, α-RANKL led to a decrease in IL-8 secretion. Recombinant human IL-8 protein reversed the effect of α-RANKL on the expression of proliferation- and apoptosis‑related molecules, and proliferation and apoptosis in the HeLa and SiHa cells. The present study suggests that a high level of mRANKL/RANK expression in cervical cancer lesions plays an important role in the rapid growth of cervical cancer cells possibly through strengthening the dialogue between cervical cancer cells and regulation of IL-8 secretion, which may be a possible target for cervical cancer therapy.

  13. Oleic acid, hydroxytyrosol and n-3 fatty acids collectively modulate colitis through reduction of oxidative stress and IL-8 synthesis; in vitro and in vivo studies.

    Science.gov (United States)

    Reddy, K Vijay Kumar; Naidu, K Akhilender

    2016-06-01

    Our recent study has demonstrated that medium chain triglycerides (MCT) and monounsaturated fatty acids potentiate the beneficial effects of fish oil on risk factors of cardiovascular disease. In the present study, we have investigated the influence of MCT or olive oil on the protective and mucosal healing ability of fish oil in ulcerative colitis using cell simulation and animal models. Caco-2 cells grown in medium chain fatty acids enriched medium has exaggerated t-butyl hydroperoxide induced cell damage, GSH depletion, and IL-1β induced IL-8 synthesis, compared to the cells grown in oleic acid & hydroxytyrosol (OT) enriched medium. Further, combined treatment of cells with eicosapentaenoic acid, docosahexaenoic acid, and OT has remarkably attenuated the cell damage, and IL-8 synthesis, compared to individual treatments. To evaluate the effect of these lipid formulations in vivo, adult Wistar rats were fed diet enriched with high amount of medium chain triglycerides (MCT), virgin olive oil, or their combination with fish oil. Colitis was induced in rats using dextran sulfate sodium (DSS) for 7days followed by 10-days of recovery period. Rats of MCT group exhibit severe disease activity, higher levels of inflammatory cytokines in the colon compared to the olive oil group. Furthermore, there was persistent body weight loss, loose stools, higher levels of inflammatory cytokines in the rats of MCT group, even after DSS was withdrawn from drinking water. Conversely, fish oil has remarkably attenuated the DSS induced alterations in both MCT and olive oil diet groups with significantly greater effect in the olive oil group. Thus, MCT increase the susceptibility to colitis through oxidative damage and IL-8 synthesis in intestinal epithelial cells. The beneficial effects of virgin olive oil could be partially attributed to hydroxytyrosol. Combined treatment of hydroxytyrosol, oleic acid and n-3 fatty acids exhibit huge therapeutic benefits in colitis. PMID:27016717

  14. The Cytoprotective Effects of Human Endothelial Progenitor Cell-Conditioned Medium Against an Ischemic Insult Are Not Dependent on VEGF and IL-8.

    Science.gov (United States)

    Di Santo, Stefano; Fuchs, Anna-Lena; Periasamy, Ramesh; Seiler, Stefanie; Widmer, Hans Rudolf

    2016-01-01

    Endothelial progenitor cells (EPCs) promote revascularization and tissue repair mainly by paracrine actions. In the present study, we investigated whether EPC-secreted factors in the form of conditioned medium (EPC-CM) can protect cultured brain microvascular endothelial cells against an ischemic insult. Furthermore, we addressed the type of factors that are involved in the EPC-CM-mediated functions. For that purpose, rat brain-derived endothelial cells (rBCEC4 cell line) were exposed to EPC-CM pretreated with proteolytic digestion, heat inactivation, and lipid extraction. Moreover, the involvement of VEGF and IL-8, as canonical angiogenic factors, was investigated by means of neutralizing antibodies. We demonstrated that EPC-CM significantly protected the rBCEC4 cells against an ischemic insult mimicked by induced oxygen-glucose deprivation followed by reoxygenation. The cytoprotective effect was displayed by higher viable cell numbers and reduced caspase 3/7 activity. Heat inactivation, proteolytic digestion, and lipid extraction resulted in a significantly reduced EPC-CM-dependent increase in rBCEC4 viability, tube formation, and survival following the ischemic challenge. Notably, VEGF and IL-8 neutralization did not affect the actions of EPC-CM on rBCEC4 under both standard and ischemic conditions. In summary, our findings show that paracrine factors released by EPCs activate an angiogenic and cytoprotective response on brain microvascular cells and that the activity of EPC-CM relies on the concerted action of nonproteinaceous and proteinaceous factors but do not directly involve VEGF and IL-8. PMID:26776768

  15. Effect of Helicobacter pylori and its virulence factors on portal hypertensive gastropathy and interleukin (IL-8, IL-10, and tumor necrosis factor-alpha levels

    Directory of Open Access Journals (Sweden)

    Zaigham Abbas

    2014-01-01

    Full Text Available Background/Aim: We aimed to assess the influence of Helicobacter pylori and its virulent factors, cytotoxin associated gene (cag A and E, on portal hypertensive gastropathy (PHG and the levels of interleukin (IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α. Patients and Methods: The patients with cirrhosis underwent screening endoscopy and the lesions related to PHG were graded. Biopsies were obtained for histology, and polymerase chain reaction (PCR of H. pylori 16S rRNA, cagA, cagE, and tissue cytokine levels was carried out. Absent or mild PHG was compared with moderate to severe PHG. Results: One hundred and forty patients with cirrhosis were studied; males numbered 92 and the mean age of the patients was 50.3 ± 12.0 years, H. pylori positivity in 87 (62.1% patients was associated with male gender (P = 0.032, younger age (P = 0.029, hepatitis D etiology (P = 0.005, higher serum albumin (0.000, lower Child Pugh score (P = 0.001, and lower portal vein diameter (P = 0.001. There was no significant difference in the levels of TNF-α and IL-8. However, a decrease in the anti-inflammatory cytokine IL-10 was noted with moderate to severe gastropathy. Four H. pylori strains were positive for both cagA and cagE, while four were positive for cagA only. All the four patients with both virulent factors had mild gastropathy only. Conclusion: The presence of H. pylori infection neither affected the severity of PHG nor augmented the IL-8 and TNF-α levels. There was a decline of virulent H. pylori strains and IL-10 levels in patients with advanced PHG.

  16. Effect of Helicobacter pylori and its Virulence Factors on Portal Hypertensive Gastropathy and Interleukin (IL)-8, IL-10, and Tumor Necrosis Factor-alpha Levels

    Science.gov (United States)

    Abbas, Zaigham; Yakoob, Javed; Usman, Muhammad W.; Shakir, Tanzila; Hamid, Saeed; Jafri, Wasim

    2014-01-01

    Background/Aim: We aimed to assess the influence of Helicobacter pylori and its virulent factors, cytotoxin associated gene (cag) A and E, on portal hypertensive gastropathy (PHG) and the levels of interleukin (IL)-8, IL-10, and tumor necrosis factor-alpha (TNF-α). Patients and Methods: The patients with cirrhosis underwent screening endoscopy and the lesions related to PHG were graded. Biopsies were obtained for histology, and polymerase chain reaction (PCR) of H. pylori 16S rRNA, cagA, cagE, and tissue cytokine levels was carried out. Absent or mild PHG was compared with moderate to severe PHG. Results: One hundred and forty patients with cirrhosis were studied; males numbered 92 and the mean age of the patients was 50.3 ± 12.0 years, H. pylori positivity in 87 (62.1%) patients was associated with male gender (P = 0.032), younger age (P = 0.029), hepatitis D etiology (P = 0.005), higher serum albumin (0.000), lower Child Pugh score (P = 0.001), and lower portal vein diameter (P = 0.001). There was no significant difference in the levels of TNF-α and IL-8. However, a decrease in the anti-inflammatory cytokine IL-10 was noted with moderate to severe gastropathy. Four H. pylori strains were positive for both cagA and cagE, while four were positive for cagA only. All the four patients with both virulent factors had mild gastropathy only. Conclusion: The presence of H. pylori infection neither affected the severity of PHG nor augmented the IL-8 and TNF-α levels. There was a decline of virulent H. pylori strains and IL-10 levels in patients with advanced PHG. PMID:24705150

  17. Biocompatible micro-sized cell culture chamber for the detection of nanoparticle-induced IL8 promoter activity on a small cell population

    Directory of Open Access Journals (Sweden)

    Oostingh Gertie

    2011-01-01

    Full Text Available Abstract In most conventional in vitro toxicological assays, the response of a complete cell population is averaged, and therefore, single-cell responses are not detectable. Such averaging might result in misinterpretations when only individual cells within a population respond to a certain stimulus. Therefore, there is a need for non-invasive in vitro systems to verify the toxicity of nanoscale materials. In the present study, a micro-sized cell culture chamber with a silicon nitride membrane (0.16 mm2 was produced for cell cultivation and the detection of specific cell responses. The biocompatibility of the microcavity chip (MCC was verified by studying adipogenic and neuronal differentiation. Thereafter, the suitability of the MCC to study the effects of nanoparticles on a small cell population was determined by using a green fluorescence protein-based reporter cell line. Interleukin-8 promoter (pIL8 induction, a marker of an inflammatory response, was used to monitor immune activation. The validation of the MCC-based method was performed using well-characterized gold and silver nanoparticles. The sensitivity of the new method was verified comparing the quantified pIL8 activation via MCC-based and standard techniques. The results proved the biocompatibility and the sensitivity of the microculture chamber, as well as a high optical quality due to the properties of Si3N4. The MCC-based method is suited for threshold- and time-dependent analysis of nanoparticle-induced IL8 promoter activity. This novel system can give dynamic information at the level of adherent single cells of a small cell population and presents a new non-invasive in vitro test method to assess the toxicity of nanomaterials and other compounds. PACS: 85.35.Be, 81.16.Nd, 87.18.Mp

  18. Biocompatible micro-sized cell culture chamber for the detection of nanoparticle-induced IL8 promoter activity on a small cell population

    Science.gov (United States)

    Kohl, Yvonne; Oostingh, Gertie J.; Sossalla, Adam; Duschl, Albert; von Briesen, Hagen; Thielecke, Hagen

    2011-08-01

    In most conventional in vitro toxicological assays, the response of a complete cell population is averaged, and therefore, single-cell responses are not detectable. Such averaging might result in misinterpretations when only individual cells within a population respond to a certain stimulus. Therefore, there is a need for non-invasive in vitro systems to verify the toxicity of nanoscale materials. In the present study, a micro-sized cell culture chamber with a silicon nitride membrane (0.16 mm2) was produced for cell cultivation and the detection of specific cell responses. The biocompatibility of the microcavity chip (MCC) was verified by studying adipogenic and neuronal differentiation. Thereafter, the suitability of the MCC to study the effects of nanoparticles on a small cell population was determined by using a green fluorescence protein-based reporter cell line. Interleukin-8 promoter (pIL8) induction, a marker of an inflammatory response, was used to monitor immune activation. The validation of the MCC-based method was performed using well-characterized gold and silver nanoparticles. The sensitivity of the new method was verified comparing the quantified pIL8 activation via MCC-based and standard techniques. The results proved the biocompatibility and the sensitivity of the microculture chamber, as well as a high optical quality due to the properties of Si3N4. The MCC-based method is suited for threshold- and time-dependent analysis of nanoparticle-induced IL8 promoter activity. This novel system can give dynamic information at the level of adherent single cells of a small cell population and presents a new non-invasive in vitro test method to assess the toxicity of nanomaterials and other compounds. PACS: 85.35.Be, 81.16.Nd, 87.18.Mp

  19. Differential gene expression during capillary morphogenesis in a microcarrier-based three-dimensional in vitro model of angiogenesis with focus on chemokines and chemokine receptors

    Institute of Scientific and Technical Information of China (English)

    Xi-Tai Sun; Min-Yue Zhang; Chang Shu; Qiang Li; Xiao-Gui Yan; Ni Cheng; Yu-Dong Qiu; Yi-Tao Ding

    2005-01-01

    AIM: To globally compare the gene expression profiles during the capillary morphogenesis of human microvascular endothelial cells (HMVECs) in an in vitro angiogenesis system with affymetrix oligonucleotide array.METHODS: A microcarrier-based in vitro angiogenesis system was developed, in which ECs migrated into the matrix,proliferated, and formed capillary sprouts. The sprouts elongated, branched and formed networks. The total RNA samples from the HMVECs at the selected time points (0.5,24, and 72 h) during the capillary morphogenesis were used for microarray analyses, and the data were processed with the softwares provided by the manufacturers. The expression patterns of some genes were validated and confirmed by semi-quantitative RT-PCR. The regulated genes were grouped based on their molecular functions and expression patterns, and among them the expression of chemokines and chemokine receptors was specially examined and their functional implications were analyzed.RESULTS: A total of 1 961 genes were up- or downregulated two-folds or above, and among them, 468 genes were up- or down-regulated three-folds or above. The regulated genes could be grouped into categories based on their molecular functions, and were also clustered into six groups based on their patterns of expression. As for chemokines and chemokine receptors, CXCL1/GRO-α,CXCL2/GRO-β, CXCLS/ENA-78, CXCL6/GCP2, IL-8/CXCL8,CXCL12/SDF-1, CXCL9/Mig, CXC11/ITAC, CX3CL1/fractalkine,CCL2/MCP-1, CCL3, CCLS/RANTES, CCL7, CCL15, CCL21,CCL23, CCL28, and CCR1, CCR9, CXCR4 were identified.Moreover, these genes demonstrated different changing patterns during the capillary morphogenesis, which implied that they might have different roles in the sequential process. Among the chemokines identified, CCL2/MCP-1,CCL5/RANTES and CX3CL1 were specially up-regulated at the 24-h time point when the sprouting characterized the morphological change. It was thus suggested that they might exert crucial roles at the early stage

  20. Presence of terminal EPIYA phosphorylation motifs in Helicobacter pylori CagA contributes to IL-8 secretion, irrespective of the number of repeats.

    OpenAIRE

    Papadakos, Konstantinos S.; Sougleri, Ioanna S; Mentis, Andreas F; Efstathios Hatziloukas; Sgouras, Dionyssios N.

    2013-01-01

    CagA protein contributes to pro-inflammatory responses during H. pylori infection, following its intracellular delivery to gastric epithelial cells. Here, we report for the first time in an isogenic background, on the subtle role of CagA phosphorylation on terminal EPIYA-C motifs in the transcriptional activation and expression of IL-8. We utilized isogenic H. pylori mutants of P12 reference strain, expressing CagA with varying number of EPIYA-C motifs and the corresponding phosphorylation de...

  1. Atypical chemokine receptors in cancer: friends or foes?

    Science.gov (United States)

    Massara, Matteo; Bonavita, Ornella; Mantovani, Alberto; Locati, Massimo; Bonecchi, Raffaella

    2016-06-01

    The chemokine system is a fundamental component of cancer-related inflammation involved in all stages of cancer development. It controls not only leukocyte infiltration in primary tumors but also angiogenesis, cancer cell proliferation, and migration to metastatic sites. Atypical chemokine receptors are a new, emerging class of regulators of the chemokine system. They control chemokine bioavailability by scavenging, transporting, or storing chemokines. They can also regulate the activity of canonical chemokine receptors with which they share the ligands by forming heterodimers or by modulating their expression levels or signaling activity. Here, we summarize recent results about the role of these receptors (atypical chemokine receptor 1/Duffy antigen receptor for chemokine, atypical chemokine receptor 2/D6, atypical chemokine receptor 3/CXC-chemokine receptor 7, and atypical chemokine receptor 4/CC-chemokine receptor-like 1) on the tumorigenesis process, indicating that their effects are strictly dependent on the cell type on which they are expressed and on their coexpression with other chemokine receptors. Indeed, atypical chemokine receptors inhibit tumor growth and progression through their activity as negative regulators of chemokine bioavailability, whereas, on the contrary, they can promote tumorigenesis when they regulate the signaling of other chemokine receptors, such as CXC-chemokine receptor 4. Thus, atypical chemokine receptors are key components of the regulatory network of inflammation and immunity in cancer and may have a major effect on anti-inflammatory and immunotherapeutic strategies. PMID:26908826

  2. 星形细胞瘤和髓母细胞瘤患儿血清IL-6、IL-8和MIP-1α水平变化%Urvey of the Serum Levels of IL-6, IL-8 and MIP-1α in Pediatric Brain Tumor Patients

    Institute of Scientific and Technical Information of China (English)

    刘志忠; 陈燕; 叶虹; 王红艳; 康熙雄

    2012-01-01

    Objective To explore the changes of levels of serum IL-6, IL-8 and MIP-lα in children with in-tracranial astrocytoma and medulloblastoma and their clinical values. Methods The serum concentrations of IL-6, IL-8 and MIP- lα were measured simultaneously by use of multiplexed Luminex assay in 55 children with astrocytoma, 46 children with medulloblastoma and 54 healthy children. Results The serum concentrations of IL-6, IL- 8 and MIP-1α in both astrocytoma and medulloblastoma groups were significantly higher than that in healthy controls. Moreover, there was significant difference in the serum concentration of IL-6 between the astrocytoma and medulloblastoma group (P<0. 01). Correlation analysis showed significantly positive correlation between any two cytokins among IL-6, IL-8 and MIP-1 in astrocytoma or medulloblastoma group (P<0.01). Compared with girl patients, the serum concentration of IL-6 was significantly higher in boys with astrocytoma, and the serum concentration of IL-6 and MIP-lα were significantly higher in boys with medulloblastoma (P < 0.05). Conclusion The change in the serum levels of IL-6, IL-8 and MIP-lα is closely associated with the occurrence of pediatric brain tumor. The three inflammatory factors could work together to form a totally internal function.%目的 研究星形细胞瘤和髓母细胞瘤患儿血清IL-6、IL-8和MIP-1α含量变化及临床意义.方法 应用Luminex 200多功能液相芯片分析仪检测54例健康儿童和55例星形细胞瘤、46例髓母细胞瘤患儿血清IL-6、IL-8和MIP-1α浓度.结果 两肿瘤组血清IL-6、IL-8、MIP-1α浓度均显著高于正常对照组(均P<0.01),而且星形细胞瘤组IL-6水平显著高于髓母细胞瘤组(P<0.01),两组患儿血清中三种细胞因子浓度两两正相关(均P<0.01).男、女患儿间比较,星形细胞瘤组只有IL-6水平差异具有统计学意义(P<0.05);髓母细胞瘤组IL-6、MIP-1a水平差异均有统计学意义(均P<0.05).

  3. 幽门螺杆菌毒素相关蛋白A的EPIYA多态性对胃上皮细胞AGS形态及IL-8表达的影响%Effects of the Patterns of Helicobacter pylori CagA EPIYA Motifs on AGF Cell Morphology and IL-8 Secretion Levels

    Institute of Scientific and Technical Information of China (English)

    刘鹿; 王艳春; 陶好霞; 袁盛凌; 王令春; 刘纯杰

    2015-01-01

    Objective: To investigate the effects of the patterns of EPIYA motifs of Helicobacter pylori cytotoxin-associated gene A(CagA) on the cell morphology and the IL-8 secretion levels of AGS cells. Methods: The differ⁃ent genotypes of EPIYA motifs of cagA were designed and the codons were humanized, then the synthetic frag⁃ments were assembled and constructed into pcDNA3.1 vector. The recombinants were transfected into AGS cells and the effects of patterns of EPIYA motifs of CagA on cell morphology and the IL-8 secretion levels were ob⁃served. Results: Cellular morphological observation was conducted every 6 h after the transfection, and the num⁃bers of hummingbird-like cells were counted at 24 and 36 h respectively. The statistical results showed that all CagA genotypes could increase the number of cells with hummingbird-like change. Compared with the mock-vehi⁃cle controls, all the six CagA types showed a remarkably significant differences; compared with CagA ABCCC, the five CagA types left showed a remarkably significant differences. In addition, IL-8 secreted by these cells 12 and 36 h after transfection was detected respectively. The statistical analysis revealed that, at 12 h after transfection, the secretion of IL-8 began to appear difference among the six CagA types; at 36 h after transfection, compared with the mock-vehicle controls, CagA ABD, CagA J-Western, CagA ABDD and CagA ABCCC showed a remark⁃ably significant differences. Although both CagA ABD and CagA ABDD belonged to East Asian type, they had sig⁃nificantly different effects on the IL-8 secretion levels of AGS cells. Meanwhile, both CagA ABC and CagA ABCCC which belonged to Western type had significantly different effects on the IL-8 secretion levels too. Con⁃clusion: CagA virulent factor of H.pylori caused cell hummingbird phenotype and increased the IL-8 secretion lev⁃els of AGS cells. The number of EPIYA-C motif was positively correlated with hummingbird-cell formation, and the

  4. 过表达白细胞介素8促进乳腺癌BT549细胞迁移%Overexpression of IL-8 promotes migration of BT549 breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    邓芳; 王静; 范梦恬; 郭杨柳; 李亚; 施琼

    2016-01-01

    目的 构建含有白细胞介素8(IL-8)基因的重组腺病毒,并观察其对BT549乳腺癌细胞增殖、细胞周期以及迁移能力的影响.方法 以143B细胞cDNA为模版,PCR扩增IL-8基因,与穿梭质粒pAdTrack-TO4连接,构建重组穿梭质粒pAdTrack-TO4-IL-8,由PmeⅠ线性化并电转入AdEasier细菌中,获得重组腺病毒质粒pAdIL-8,PacI酶切经LipofectamineTM 2000介导转入HEK293细胞进行包装扩增,检测滴度;反转录PCR检测BT549细胞中IL-8 mRNA的水平,ELISA检测BT549细胞培养上清液中IL-8的水平;流式细胞术检测细胞周期情况;MTT法检测细胞增殖能力;划痕愈合实验检测细胞迁移能力.结果 PCR以及测序证实pAdTrack-TO4-IL-8构建成功;pAdIL-8经酶切证实重组正确;重组腺病毒AdIL-8感染BT549细胞,可高表达IL-8.过表达IL-8的BT549细胞迁移能力增强,但其增殖活性无明显变化、将细胞周期阻滞于S期.结论 过表达IL-8可促进BT549细胞的迁移.

  5. Clinical Significance of Changes on Serum TGF-Ⅱ, IL-8 and TNF-α Levels in Patients with Acute Cerebral Infarction%ACI患者血清IGF-Ⅱ、IL-8和TNF-α水平的变化及临床意义

    Institute of Scientific and Technical Information of China (English)

    朱德义; 刘家喜

    2012-01-01

    Objective To explore the clinical significance of changes on serum ICF- Ⅱ ,IL-8 and TNF-α levels in patients with a-cute cerebral infaction. Methods Serum IGF-Ⅱ ,IL-S and TNF-α levels were determined with radioimmunoassay(RIA)in 33 patients with acute cerebral infarction and 35 normal controls. ReslutS The serum IGF- Ⅱ ,IL-8 and TNF-α in patients with acute cerebral infarction were significantly higher than those in controls (P<0.01) , the serum IGF- Ⅱ levels were positive correlation with serum IL-8, TNF-a levels (r =0.5712, 0.6018, P<0.01 ). Conclusion Detection of changes of serum IGF- Ⅱ, IL-8and TNF-α levels can be help to assess the progress and prognosis of the disease, also such laboratory items offer to realise the pathosis and therapeutic effect possess definite clinical value.%目的:探讨急性脑梗死(ACI)患者血清IGF-Ⅱ、IL-8和TNF-α水平的变化及临床意义.方法:采用放射免疫分析对33例ACI患者进行了血清IGF-Ⅱ、IL-2和TNF-α检测,并与35名正常健康人作比较.结果:ACI患者血清IGF-Ⅱ、IL-2和TNF-α水平均非常显著地高于正常人组(P<0.01),且血清IGF-Ⅱ水平与IL-8和TNF-α水平呈正相关(r=0.5712、0.6018,P<0.01).结论:检测ACI患者血清IGF-Ⅱ、IL-2和TNF-α水平变化,对观察疾病的预后和疗效具有确切的临床价值.

  6. 细胞因子IL-8、IL-12和TNF-α对肝硬化失代偿发生的意义%Level of cytokines IL-8 and IL-12 and TNF-α on lost of compensation of liver cirhosis

    Institute of Scientific and Technical Information of China (English)

    罗丕丹; 唐进先; 麦昌季

    2009-01-01

    目的 探讨与肝脏损害有关的细胞因子IL-8、IL012和TNF-α的变化在不同时期的肝硬化及不同肝功能状况的关系,以期阐明细胞因子检测在肝硬化失代偿发生临床意义和部分机制.方法 研究选用肝硬化代偿期患者17例、失代偿期32例、肝硬化失代偿期合并自发性腹膜炎13例,共计62例;分别测定其静脉血血浆中IL-8、IL-12和TNF-α含量.检测采用ELISA方法.分析细胞因子在不同时期的肝硬化及不同肝功能状况的关系.结果 细胞因子IL-8、IL-12和TNF-α在各组肝硬化患者均有不同程度的升高.且升高的程度与肝硬化患者病情的严重程度相一致.结论 细胞因子升高的幅度与Child-Pugh分级标准评估的肝功能严重程度成正比.%Objective To observe the correlation of variations of levels of cytokines IL-8,TNF-α and IL-12 with cirrhosis patients. Methods There 62 cirrhosis patients were collected and the leveles of IL-8,IL-12,TNF-α were determined by ELISA. Results The levies of IL-8, IL-12 and TNF-α in patients of every group were increased in accordance with the severity of cirrhosis. Conclusion The increase of cytokines was consistent with the severity of liver function.

  7. 乳腺癌患者手术治疗前后血清CA153、IL-8、MMP-2和TIMP-2水平检测的临床意义%Clinical significance of serum level of CA153,IL-8,MMP-2,TIMP-2 changes of patients with breast cancer before and after surgical treatment

    Institute of Scientific and Technical Information of China (English)

    王仲

    2013-01-01

    目的 探讨乳腺癌患者手术治疗前后血清糖类抗原-153 (CA153)、白细胞介素-8(IL-8)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-2组织抑制剂(TIMP-2)的含量及临床价值.方法 应用放射免疫分析法和酶联法对34例乳腺癌患者(观察组)进行手术治疗前后血清CA153、IL-8和MMP-2、TIMP-2水平的检测,并与35例正常对照组作比较.结果 观察组在手术前血清CA153、IL-8、MMP-2、TIMP-2均显著高于对照组(P<0.01);手术后3个月未复发的29例其血清CA153、IL-8和MMP-2、TIMP-2水平下降或接近正常,而复发的5例其血清水平又回升到手术前的水平(P<0.01);且血清CA153水平与IL-8、MMP-2 、TIMP-2测定显著相关(r=0.5784、0.4926、0.6011,P<0.01).结论 检测乳腺癌患者手术治疗前后血清CA153、IL-8、MMP-2、TIMP-2水平的变化可作为乳腺癌患者诊断和疗效观察的参数.

  8. Effect of psychological nursing on expression levels of serum TNF-α, IL-6 and IL-8 in patients after breast cancer operation%心理护理对乳腺癌术后患者血清中TNF-α、IL-6和IL-8蛋白表达水平的影响

    Institute of Scientific and Technical Information of China (English)

    程光文

    2014-01-01

    目的:观察心理护理对乳腺癌术后患者血清中TNF-α、IL-6和IL-8蛋白表达水平的影响.方法:将70例乳腺癌患者随机分为常规护理组和心理护理组各35例,两组乳腺癌患者均于术后第1天采血及术后第7天采血;选择同期体检健康妇女20例作为正常对照组.采用ELISA方法检测血清中TNF-α、IL-6和IL-8的蛋白含量,采用实时荧光定量法检测TNF-α、IL-6和IL-8 mRNA的表达水平.结果:与术后第1天相比较,术后第7天常规护理组TNF-α、IL-6和IL-8的蛋白含量及mRNA的表达水平均降低,差异有统计学意义(P<0.05),术后第7天心理护理组TNF-α、IL-6和IL-8的蛋白含量及mRNA的表达水平均明显降低,差异有统计学意义(P<0.01);术后第7天常规护理组TNF-α、IL-6和IL-8的蛋白含量及mRNA的表达水平仍高于心理护理组,差异有统计学意义(P<0.05).结论:心理护理能进一步降低乳腺癌患者血清中炎性因子的表达水平,从而增强患者免疫力及提高术后生活质量.

  9. 血清IL-8和sApo-1/Fas与乳腺癌患者临床病理学参数的关系%Correlationship between the Serum IL-8 and Soluble Apo-1/Fas and the Clinicopathological Parameters in Patient with Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    郑天郢; 王永刚; 张昕

    2005-01-01

    目的:探讨外周血IL-8和sFas在不同绝经状态、不同雌激素受体状态(ER)、不同转移情况的乳腺癌术后复发及转移患者中的表达及其临床意义.方法:采用酶联免疫双抗体夹心法检测94例乳腺癌术后复发及转移患者和30例正常人的血清IL-8和sFas水平,并比较它们与绝经状态、ER状态、不同转移情况的关系以及化疗对其影响.结果:1)乳腺癌患者血清IL-8及sFas水平明显高于正常人(P<0.05).2)血清IL-8与雌激素受体(ER)状态和骨转移关系密切:ER(-)者高于ER(+)者(P<0.05);有骨转移者高于局部复发及/或区域淋巴结转移(P<0.01)以及肝、肺转移者(P<0.05).3)血清sFas水平与绝经状态及肝、肺转移关系密切:绝经后患者高于绝经前患者(P<0.05);有肝、肺转移者高于局部复发及/或区域淋巴结转移(P<0.01)以及骨转移者(P<0.05).4)化疗后血清sFas水平较化疗前下降(P<0.05),而血清IL-8无明显变化.结论:血清IL-8和sFas水平与乳腺癌患者的生物学行为及预后有一定关系,值得进一步研究.

  10. Microbiological exploitation of the chemokine system

    DEFF Research Database (Denmark)

    Holst, Peter J; Rosenkilde, Mette M

    2003-01-01

    Several viruses encode chemokine elements in their genome. This review focuses on the roles of such elements in the ongoing battle between the virus and the host. The biological and pharmacological characterizations of several of these chemokine elements have highlighted their importance in the m...

  11. Cascading Cosmology

    CERN Document Server

    Agarwal, Nishant; Khoury, Justin; Trodden, Mark

    2009-01-01

    We develop a fully covariant, well-posed 5D effective action for the 6D cascading gravity brane-world model, and use this to study cosmological solutions. We obtain this effective action through the 6D decoupling limit, in which an additional scalar degree mode, \\pi, called the brane-bending mode, determines the bulk-brane gravitational interaction. The 5D action obtained this way inherits from the sixth dimension an extra \\pi self-interaction kinetic term. We compute appropriate boundary terms, to supplement the 5D action, and hence derive fully covariant junction conditions and the 5D Einstein field equations. Using these, we derive the cosmological evolution induced on a 3-brane moving in a static bulk. We study the strong- and weak-coupling regimes analytically in this static ansatz, and perform a complete numerical analysis of our solution. Although the cascading model can generate an accelerating solution in which the \\pi field comes to dominate at late times, the presence of a critical singularity prev...

  12. 硫化氢对幽门螺杆菌感染GES-1细胞CSE,NF-κB及IL-8 mRNA表达的影响%Effect of hydrogen sulifde on the expression of CSE, NF-κB, and IL-8 mRNA in GES-1 cells withHelicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    徐灿霞; 万迎春; 郭涛; 陈雄

    2013-01-01

    Objective: To investigate the effect of hydrogen sulifde (H2S) on the expression of CSE, NF-κB, and IL-8 mRNA in GES-1 cells withHelicobacter pylori (H. pylori) infection and to explore its mechanism on gastric mucosa inlfammation caused byH. pylori. Methods: GES-1 cells were cultured for 24 h and divided into a control group (neitherH. pylori nor NaHS), anH. pylori group, a NaHS group (which was further divided into 4 groups at 50, 100, 200, or 400 μmol/L NaHS), andH. pylori + NaHS group (which was further divided into 4 groups at 50, 100, 200, or 400 μmol/L NaHS). Each group was then cultured for 3, 6, or 12 h. The expression of CSE, NF-κB, and IL-8 mRNA was measured by RT-PCR, and their correlation was analyzed. Results: The expression of CSE, NF-κB, and IL-8 mRNA in GES-1 cells in theH. pylori group was higher than that in the control group. The expression of CSE in the 200 μmol/L NaHS group and 400 μmol/L NaHS group was lower than that of the control group (P0.05). The expression of CSE, NF-κB, and IL-8 mRNA in all groups of NaHS,H. pylori + 200 μmol/L NaHS group, andH. pylori + 400 μmol/L NaHS group was lower than that in theH. pylori group (P Conclusion:H. pylori can induce NF-κB and IL-8 mRNA expression and upregulate CSE mRNA expression. At 200 and 400 μmol/L, NaHS can suppressH. pylori-induced NF-κB and IL-8 mRNA expression and ameliorate the morphology ofH. pylori-induced GES-1 injury, which may protect gastric epithelial cells byH. pylori infection.%目的:观察硫化氢(hydrogen sulfide,H2S)对幽门螺杆菌(H. pylori)感染的GES-1细胞CSE,NF-κB及IL-8 mRNA表达及其形态学的影响,探讨其对H. pylori所致胃黏膜细胞炎症的作用及机制。方法:将GES-1细胞培养24 h后分为对照组(不加H. pylori及NaHS)、H. pylori组、NaHS组(又分为4个亚组,分别加入50,100,200或400μmol/L NaHS)和H. pylori + NaHS组(又分为4个亚组,分别加入H. pylori与50,100,200或400μmol/L Na

  13. Uncaria tomentosa alkaloidal fraction reduces paracellular permeability, IL-8 and NS1 production on human microvascular endothelial cells infected with dengue virus.

    Science.gov (United States)

    Lima-Junior, Raimundo Sousa; Mello, Cintia da Silva; Siani, Antonio Carlos; Valente, Ligia M Marino; Kubelka, Claire Fernandes

    2013-11-01

    Dengue is the major Arbovirus in the world, annually causing morbidity and death. Severe dengue is associated with changes in the endothelial barrier function due to the production of inflammatory mediators by immune cells and by the endothelium. Dengue virus (DENV) replicates efficiently in human endothelial cells in vitro and elicits immune responses resulting in endothelial permeability. Uncaria tomentosa (Willd.) DC.(Rubiaceae), known as cat's claw, has been used in folk medicine for the treatment of a wide-array of symptoms, and several scientific studies reported its antiviral, immunomodulatory, anti-inflammatory and antioxidant properties. Here we infected a human lineage of dermal microvascular endothelial cells (HMEC-1) with DENV-2 and treated it with an alkaloidal fraction from U. tomentosa bark (AFUT). We showed antiviral and immunomodulatory activities of U. tomentosa by determining the NS1 antigen and IL-8 in supernatant of DENV-2 infected HMEC-1. Furthermore, by measurement of transendothelial electrical resistance (TEER) we demonstrated, for the first time, that a plant derivative contributed to the reduction of paracellular permeability in DENV-2 infected HMEC-1. We also showed that IL-8 contributed significantly to the induction of permeability. Although further investigations should be conducted before a new drug can be suggested, our in vitro data support evidence that AFUT could be potentially useful in developing a treatment for severe dengue.

  14. 小儿急性细菌性脑膜炎患者趋化因子CXCL-5和IL-8的表达

    Institute of Scientific and Technical Information of China (English)

    曹其运; 董忠生

    2006-01-01

    细菌性脑膜炎主要病理生理特征是外周血和脑脊液(CSF)中有大量的中性粒细胞浸润或聚集,这些感染后的机体反应对清除细菌感染起着重要的作用,然而免疫反应也诱导了局部(脑脊膜)的炎症损伤。CXCL-5和IL-8是诱导中性粒细胞激活和移动的重要趋化因子。作者通过检测小儿急性细菌性脑膜炎患者外周血和脑脊液中CXCL-5和IL-8水平变化,旨在探讨它们在疾病发生过程中的作用。

  15. Classical swine fever virus infection modulates serum levels of INF-α, IL-8 and TNF-α in 6-month-old pigs.

    Science.gov (United States)

    von Rosen, T; Lohse, L; Nielsen, J; Uttenthal, Å

    2013-12-01

    Several studies have highlighted the important role of cytokines in disease development of classical swine fever virus (CSFV) infection. In the present study, we examined the kinetics of 7 porcine cytokines in serum from pigs infected with 3 different CSFV strains. Based on the clinical picture in 6-month-old Danish pigs, the strains used for inoculation were classified as being of low (Bergen), low to moderate (Eystrup) and moderate to high (Lithuania) virulence. The cytokines interferon-alpha (INF-α), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) showed increased levels after CSFV infection with more or less comparable course in the 3 groups. However, the cytokine level peaked with a 2-3 days delay in pigs infected with the low virulent strain compared to those infected with a moderately or highly virulent strain. These findings may indicate that INF-α, IL-8 and TNF-α are involved in the immune response during CSFV infection with strains of different virulence.

  16. Blood Serum Levels of IL-2, IL-6, IL-8, TNF-α and IL-1β in Patients on Maintenance Hemodialysis

    Institute of Scientific and Technical Information of China (English)

    Jacek Rysz; Maciej Banach; Aleksandra Cialkowska-Rysz; Robert Stolarek; Marcin Barylski; Jaroslaw Drozdz; Piotr Okonski

    2006-01-01

    Cytokines are essential mediators of immune response and inflammatory reactions. Patients with chronic renal failure (CRF) commonly present with abnormalities of immune function related with impaired kidney function and the accumulation of uremic toxins in addition to bioincompatibility of dialyzer membranes. During a hemodialysis (HD) session, cytokines are released mainly by monocytes activated by endotoxin-type compounds in dialyzer fluid,complement factors and direct contact with dialyzer membrane. The study included 15 CRF patients, aged 36.4 ± 2.9 years, on regular HD maintenance therapy for mean 68 ± 10 months and 15 healthy controls. It was designed to assess serum levels of a panel of inflammatory cytokines: IL-1β, IL-2, IL-6, IL-8 and TNF-α in CRF patients on regular maintenance HD before, 20, 60 and 240 minutes of a single HD session in parallel with C-reactive protein (CRP) as an additional parameter. CRP concentration was increased in HD patients when compared with healthy controls. The concentrations of IL-1, IL-6, IL-8 and TNF-α were increased, whereas the serum level of IL-2 was not altered during a single HD session.

  17. Role of chemokines in the pathogenesis of rheumatoid synovitis

    Directory of Open Access Journals (Sweden)

    N. Pipitone

    2011-09-01

    Full Text Available Chemokines play a central role in the pathogenesis of rheumatoid arthritis (RA synovitis which is characterised by new blood vessel formation, thickening of the lining layer and infiltration of immune cells. The inflammatory infiltrate is generated by a series of events which include the recruitment of leukocytes from the blood stream into the tissue, their local retention and activation to effector cells. All these processes are finely regulated by the interplay of different cell adhesion molecules (CAMs and chemoattractant factors called chemokines (CK. CK are a superfamily of small proteins that play a crucial role in immune and inflammatory reactions. These chemoattractant cytokines share structural similarities including four conserved cysteine residues which form disulphide bonds in the tertiary structure of the proteins. CK mediate their effects by binding specific receptors (CK-R characterised by a domain structure which spans the cell membrane seven times and signal through heterotrimeric GPT-binding proteins. Activation of the CK network results in an amplification of the inflammatory cascade and consequently in the progressive destruction of RA joints. The recognition of the central role of CK in inflammation has paved the way to the development of new agents capable of interfering with CK and CK-R. This review will focus in particular on the role of CK in regulating leukocyte trafficking in RA joints.

  18. 乌司他丁对重症急性胰腺炎大鼠IL-8及TNF-α的影响%Effects of Ulinastatin on the Expressions of IL-8 and TNF-α in Rats with Severe Acute Pancreatitis

    Institute of Scientific and Technical Information of China (English)

    董桂军; 田广平; 尹学永; 马林升

    2013-01-01

    Objective To study the effects of ulinastatin on the expressions of IL-8 and TNF-α in rats with severe acute pancreatitis.Methods Ninety healthy male SD rats were divided into three groups:blank control group (30 rats),SAP group (30 rats) and ulinastatin treatment group (30 rats).Each group was divided into three subgroups:6h group,12h group and 24h group.SAP model was established by injecting 5% sodiumtauro cholate via retrograde bile and pancreaticduct.The treatment groups were injected with ulinastatin via hepatic portal vein.The blank control group and SAP group was injected with physiological saline.Pathological changes were performed with the aid of hematoxylin-eosin staining.Detect the changes of serum amylase,IL-8 and TNF-α in different groups.Results Compared to the SAP group,the rats in ulinastatin treatment group had a lower pathological damage,the level of serum amylase,IL-8 and TNF-αwere significantly decreased in ulinastatin treatment groups (P<0.05).Conclusion Ulinastatin can ameliorate the pathological damage in rats of SAP.The effect of ulinastatin on SAP may be related to decreasing the expressions of IL-8 and TNF-α.%目的 探讨乌司他丁对重症急性胰腺炎(SAP)大鼠IL-8及TNF-α表达的影响.方法 90只清洁级健康雄性SD大鼠随机分为3组:正常对照组、SAP模型组、乌司他丁治疗组,每组各30只.各组分为第6h、12h和24h三个亚组,每个亚组10只.利用5%牛磺胆酸钠逆行注射建立SAP模型.治疗组大鼠给予门静脉注射乌司他丁,正常对照组及模型组注射等量生理盐水.采用HE染色方法观察病理改变,并检测血清淀粉酶、IL-8及TNF-α的水平.结果 乌司他丁治疗组与SAP模型组比较,胰腺病理学改变明显减轻,血清淀粉酶、IL-8及TNF-α的表达水平明显降低(P<0.05).结论 乌司他丁可以减轻SAP大鼠胰腺的病理改变,其作用可能与下调IL-8及TNF-α的表达有关.

  19. 脑胶质瘤患者血清IL-6、IL-8、IL-10和TNF-α的表达及临床意义%The Expression of IL-6, IL-8, IL-10 and TNF-α in Serum of Glioma and Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    李春生; 张朋军

    2013-01-01

    [Purpose] To explore the diagnostic value of serum interleukin-6 (IL-6), IL-8, IL-10 and tumor necrosis factor (TNF-α) for glioma. [Materials and methods] The content of IL-6, IL-8, IL-10 and TNF-α in the healthy control group, the low-grade gliomas group and the high-grade gliomas group were detected by Luminex 200. [Results] Compared to the healthy control group, IL-6, IL-8, and TNF-α in the low-grade gliomas group showed significantly different, IL-6, IL-8, IL-10 and TNF-α in the high-level group of glioma showed significantly different. Compared to the low-grade gliomas Group, IL-6, IL-10 and TNF-α in the high-grade gliomas showed significantly different. When we discriminated the low-grade gliomas and high-grade gliomas, the best indicators was IL-10, and the diagnostic sensitivity and specificity were 74.90% and 65.80%, respectively. When the IL-6, IL-10 and TNF-α were combined, the sensitivity and specificity were 92.30% and 93.10%, respectively. [Conclusion] IL-6, IL-10 and TNF-α joint diagnostic value showed significant improvedment when compared to the individual indicators. It may provide a auxiliary method for brain the clinical diagnosis of glioma.%  [目的]探讨血清中白介素6(IL-6)、IL-8、IL-10和肿瘤坏死因子(TNF-α)对于脑胶质瘤的诊断价值。[材料与方法]分别检测健康对照组、低级别脑胶质瘤组和高级别脑胶质瘤组中IL-6、IL-8、IL-10和TNF-α的含量。[结果]与健康对照组比较,低级别脑胶质瘤组的IL-6、IL-8和TNF-α有统计学差异,高级别脑胶质瘤组的IL-6、IL-8、IL-10和TNF-α均具有统计学差异。与低级别脑胶质瘤组相比较,高级别脑胶质瘤组的IL-6、IL-10和TNF-α有统计学差异。其中区分低级别脑胶质瘤和高级别脑胶质瘤的诊断价值最好的指标为IL-10,其诊断灵敏性和特异性分别为74.90%和65.80%。IL-6、IL-10和TNF-α联合检测时其灵敏性和特异性分别为92.30%和93.10%

  20. 过敏性哮喘患者外周血IL-2、IL-4、IL-6和IL-8水平的变化%Change of the Level of IL-2, IL-4, IL-6 and IL-8 of Irritability Asthma Patients

    Institute of Scientific and Technical Information of China (English)

    王爱华; 李全新

    2000-01-01

    为了观察白细胞介素在哮喘发病中的作用,该文分别对哮喘发作期20例 ,缓解期12例患者及正常对照组10例进行了血清IL-2、IL-4、IL-6和IL-8的测定,结果发现 ,发作期患者血清IL-2水平下降,而IL-4、IL-6和IL-8水平均增高,缓解期均恢复至正常水平.提示这些细胞因子在哮喘发病过程中起着重要作用.

  1. Assessment of bone metastasis of breast cancer by radionuclide bone scan combined with CA15-3,CA50 and IL-8 on%放射性核素骨显像联合血清CA15-3、CA50、IL-8评价乳腺癌骨转移的临床意义

    Institute of Scientific and Technical Information of China (English)

    蒋炳辰; 张雪辉; 高永旺; 陈方旎; 肖国有; 姚少红

    2013-01-01

    目的 评价血清CA15-3 、CA50、IL-8联合放射性核素骨显像对乳腺癌患者骨转移诊断的临床意义.方法 利用SPECT/CT对乳腺癌患者进行骨骼放射性核素骨显像,应用化学发光法和放射免疫法对84例乳腺癌患者(均为女性)进行血清CA15-3、CA50、IL-8含量检测,并与34名正常人(均为女性)进行相关对比分析.结果 乳腺癌患者骨转移的血清CA15-3、CA50、IL-8含量水平明显高于正常人组(P<0.01),乳腺癌骨转移组灶数>2个的肿瘤标志物水平明显高于灶数≤2个的肿瘤标志物水平(P<0.01).结论 在进行放射性SPECT/CT显像同时,进行血清CA15-3、CA50和IL-8的检测,能够尽早发现乳腺癌骨转移.

  2. A Study of Relationship between Polymorphisms of Interleukin-8 and Risk of Breast Cancer in Chinese Population%IL-8基因多态性与中国人群乳腺癌关系的研究

    Institute of Scientific and Technical Information of China (English)

    刘继永; 翟祥军; 靳光付; 胡志斌; 马红霞; 钮菊英; 徐耀初; 沈洪兵

    2007-01-01

    [目的]研究IL-8(Interleukin-8)基因-251、IL-8RA+860位点基因多态性与乳腺癌发生的关系.[方法]用PCR-RFLP分析方法检测647名健康对照人群和426例乳腺癌患者的IL-8基因多态性.用Logistic回归模型计算各种基因型的乳腺癌风险(OR)及其95%可信区间.[结果]乳腺癌患者的IL-8-251AA基因型携带者患乳腺癌的风险比IL-8-251TT基因型降低了16%(OR=0.84,95%CI=0.58~1.23),而携带IL-8RA+860GC/CC基因型可以增加乳腺癌发病风险28%(OR=1.28,95%CI=0.91~1.78),但两者联系均未达到统计学显著性水平.[结论]IL-8-251和IL-8RA+860位点等位基因多态性可能与我国女性人群乳腺癌的发生存在一定的联系,值得进一步研究.

  3. 性病患者58例血清IL-2、IL-6和IL-8水平的检测及其临床意义

    Institute of Scientific and Technical Information of China (English)

    高英举

    2002-01-01

    目的探讨血清白细胞介素-2(IL-2)、白细胞介素-6(IL-6),白细胞介素-8(IL-8)在性病患者血清中水平及临床意义.方法应用双抗体夹心EliSA法检测了58例性病患者血清中IL-2、IL-6和IL-8水平.结果 58例性病患者血清中,IL-2、IL-6、IL-8水平分别为(6.4±3.2) ng/ml、(0.15±0.06) ng/ml、(0.34±0.13) ng/ml、而IL-8则显著高于正常人组(P<0.01),其中IL-2、IL-6则明显低于正常人组(P<0.01).结论性病患者的发生与发展与IL-2、IL-6降低和IL-8升高密切相关,检测IL-2、IL-6和IL-8血清水平有助于性病的判断和治疗的选择.

  4. Chemokines and their receptors in Atherosclerosis.

    Science.gov (United States)

    van der Vorst, Emiel P C; Döring, Yvonne; Weber, Christian

    2015-09-01

    Atherosclerosis, a chronic inflammatory disease of the medium- and large-sized arteries, is the main underlying cause of cardiovascular diseases (CVDs) most often leading to a myocardial infarction or stroke. However, atherosclerosis can also develop without this clinical manifestation. The pathophysiology of atherosclerosis is very complex and consists of many cells and molecules interacting with each other. Over the last years, chemokines (small 8-12 kDa cytokines with chemotactic properties) have been identified as key players in atherogenesis. However, this remains a very active and dynamic field of research. Here, we will give an overview of the current knowledge about the involvement of chemokines in all phases of atherosclerotic lesion development. Furthermore, we will focus on two chemokines that recently have been associated with atherogenesis, CXCL12, and macrophage migration inhibitory factor (MIF). Both chemokines play a crucial role in leukocyte recruitment and arrest, a critical step in atherosclerosis development. MIF has shown to be a more pro-inflammatory and thus pro-atherogenic chemokine, instead CXCL12 seems to have a more protective function. However, results about this protective role are still quite debatable. Future research will further elucidate the precise role of these chemokines in atherosclerosis and determine the potential of chemokine-based therapies. PMID:26175090

  5. An anti-inflammatory oligopeptide produced by Entamoeba histolytica down-regulates the expression of pro-inflammatory chemokines.

    Science.gov (United States)

    Utrera-Barillas, Dolores; Velazquez, Juan R; Enciso, Antonio; Cruz, Samira Muñoz; Rico, Guadalupe; Curiel-Quesada, Everardo; Teran, Luis M; Kretschmer, Roberto R

    2003-10-01

    Axenically grown Entamoeba histolytica produces a pentapeptide (Met-Gln-Cys-Asn-Ser) with anti-inflammatory properties that, among others, inhibits the in vitro and in vivo locomotion of human monocytes, sparing polymorphonuclear leucocytes from this effect [hence the name originally given. Monocyte Locomotion Inhibitory Factor (MLIF)]. A synthetic construct of this peptide displays the same effects as the native material. We now added MLIF to resting and PMA-stimulated cells of a human monocyte cell line and measured the effect upon mRNA and protein expression of pro-inflammatory chemokines (RANTES, IP-10, MIP-1alpha, MIP-1beta, MCP-1, IL-8, I-309 and lymphotactin) and the shared CC receptor repertoire. The constitutive expression of these chemokines and the CC receptors was unaffected, whereas induced expression of MIP-1alpha, MIP-1beta, and I-309, and that of the CCR1 receptor--all involved in monocyte chemotaxis--was significantly inhibited by MLIF. This suggests that the inhibition of monocyte functions by MLIF may not only be exerted directly on these cells, but also--and perhaps foremost--through a conglomerate down-regulation of endogenous pro-inflammatory chemokines.

  6. Establishment of Elevated Serum Levels of IL-10, IL-8 and TNF-β as Potential Peripheral Blood Biomarkers in Tubercular Lymphadenitis: A Prospective Observational Cohort Study

    Science.gov (United States)

    Abhimanyu; Bose, Mridula; Varma-Basil, Mandira; Jain, Ashima; Sethi, Tavpritesh; Tiwari, Pradeep Kumar; Agrawal, Anurag; Banavaliker, Jayant Nagesh; Bhowmick, Kumar Tapas

    2016-01-01

    Background Tubercular lymphadenitis (TL) is the most common form of extra-pulmonary tuberculosis (TB) consisting about 15–20% of all TB cases. The currently available diagnostic modalities for (TL), are invasive and involve a high index of suspicion, having limited accuracy. We hypothesized that TL would have a distinct cytokine signature that would distinguish it from pulmonary TB (PTB), peripheral tubercular lymphadenopathy (LNTB), healthy controls (HC), other lymphadenopathies (LAP) and cancerous LAP. To assess this twelve cytokines (Tumor Necrosis Factor (TNF)—α, Interferon (IFN) -γ, Interleukin (IL)-2, IL-12, IL-18, IL-1β, IL-10, IL-6, IL-4, IL-1Receptor antagonist (IL-1Ra), IL-8 and TNF-β, which have a role in pathogenesis of tuberculosis, were tested as potential peripheral blood biomarkers to aid the diagnosis of TL when routine investigations prove to be of limited value. Methods and Findings A prospective observational cohort study carried out during 2010–2013. This was a multi-center study with three participating hospitals in Delhi, India where through random sampling cohorts were established. The subjects were above 15 years of age, HIV-negative with no predisposing ailments to TB (n = 338). The discovery cohort (n = 218) had LNTB (n = 50), PTB (n = 84) and HC (n = 84). The independent validation cohort (n = 120) composed of patients with cancerous LAP (n = 35), other LAP (n = 20) as well as with independent PTB (n = 30), LNTB (n = 15) and HC (n = 20). Eight out of twelve cytokines achieved statistical relevance upon evaluation by pairwise and ROC analysis. Further, variable selection using random forest backward elimination revealed six serum biosignatures including IL-12, IL-4, IL-6, IL-10, IL-8 and TNF-β as optimal for classifying the LNTB status of an individual. For the sake of clinical applicability we further selected a three analyte panel (IL-8, IL-10 and TNF-β) which was subjected to multinomial modeling in the independent

  7. T. vaginalis Infection Is Associated with Increased IL-8 and TNFr1 Levels but with the Absence of CD38 and HLADR Activation in the Cervix of ESN.

    Directory of Open Access Journals (Sweden)

    Olamide D Jarrett

    Full Text Available Trichomonas vaginalis infection is associated with an increased risk of HIV infection in exposed-seronegative women (ESN despite their unique immune quiescent profile. It is important to understand possible mechanisms, such as recruitment of activated T cells, by which T. vaginalis could facilitate HIV infection in this population.We conducted a cross-sectional study exploring the relationships between T. vaginalis infection, inflammatory markers and T cell activation in the cervix of ESN. During scheduled study visits, participants completed a behavioral questionnaire and physical exam, including sexually transmitted infection (STI screening and collection of endocervical sponge and cytobrush specimens. T cell and monocyte phenotypes were measured in cervical cytobrush specimens using multi-parameter flow cytometry. Cervical sponge specimens were used to measure cytokines (IL-6, IL-8,IL-10, IP-10, RANTES using Luminex immunoassays and the immune activation marker soluble TNF receptor 1 using ELISA.Specimens of 65 women were tested. Twenty-one of these women were infected with T. vaginalis. T. vaginalis infection was associated with significantly increased concentrations of IL-8 (1275pg/ml vs. 566pg/ml, p=.02 and sTNFr1 (430 pg/ml vs. 264 pg/ml, p=.005. However, T. vaginalis infection was not associated with increased percent expression of CCR5+ T cells nor increased CD38 and HLADR activation compared to uninfected women. It was also not associated with increased expression of CCR5+ monocytes.Among ESN T. vaginalis infection is associated with increased levels of genital pro-inflammatory/immune activation markers IL-8 and TNFr1, but was not associated with an increased percentage of activated endocervical T cells along the CD38 and HLADR pathways. Thus, while T.vaginalis infection may result in some reversal of the immune quiescent profile of ESN, enhanced recruitment of activated CD38 and HLADR expressing CD4+ cells into the endocervix may not

  8. Expression of IL-8 in the breast carcinoma-associated fibroblasts before and after docetaxel treatment%多西他赛化疗对乳腺癌间质成纤维细胞IL-8表达的影响

    Institute of Scientific and Technical Information of China (English)

    荣国华; 孙梅; 宋振迪; 李洪玲

    2015-01-01

    目的 探讨分析多西他赛化疗前后白细胞介素-8(interleukin-8,IL-8)在乳腺癌间质成纤维细胞中的表达变化.方法 采集青岛市立医院乳腺外科2014-03-01-05-31未经过新辅助化疗的乳腺癌患者手术切除标本10例,通过原代培养建立稳定的乳腺癌间质成纤维细胞株.每一株原代细胞传代后分为两组.一组不做特殊处理,标记为对照组;另外一组经20 ng/mL多西他赛(泰索帝)处理24 h,标记为实验组.分别提取两组细胞的mRNA,应用Illumina光纤微珠芯片平台进行基因表达谱分析并筛选差异基因.继而通过Real-time PCR及蛋白质印迹法检测IL-8在两组乳腺癌间质成纤维细胞中的表达变化.结果 多西他赛化疗后乳腺癌间质成纤维细胞的基因表达谱发生变化,包括17例上调表达基因及18例下调表达基因(含IL-8).通过实时定量PCR及蛋白质印迹法检测发现,多西他赛化疗后乳腺癌间质成纤维细胞中的IL-8基因及蛋白表达量高于化疗前,差异有统计学意义,t=-4.274,P=0.013.结论 多西他赛化疗后乳腺癌间质成纤维细胞中IL-8表达上调,提示其可能与化疗疗效及耐药相关.

  9. In Vivo Models to Study Chemokine Biology.

    Science.gov (United States)

    Amaral, F A; Boff, D; Teixeira, M M

    2016-01-01

    Chemokines are essential mediators of leukocyte movement in vivo. In vitro assays of leukocyte migration cannot mimic the complex interactions with other cell types and matrix needed for cells to extravasate and migrate into tissues. Therefore, in vivo strategies to study the effects and potential relevance of chemokines for the migration of particular leukocyte subsets are necessary. Here, we describe methods to study the effects and endogenous role of chemokine in mice. Advantages and pitfalls of particular models are discussed and we focus on description in model's joint and pleural cavity inflammation and the effects and relevance of CXCR2 and CCR2 ligands on cell migration.

  10. Effect of glycyrrhizin on chronic urticaria patients in IL-4,IL-8,IL-17 and IL-22%18-β甘草酸苷对慢性荨麻疹患者血清中IL-4、IL-8、IL-17和IL-22的影响

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    目的:通过对18-β甘草酸苷治疗前后慢性荨麻疹患者血清中IL-4、IL-8、IL-17和IL-22的检测,探讨甘草酸苷治疗慢性荨麻疹的作用机制。方法:用Western blot检测法分别检测20例慢性荨麻疹患者经甘草酸苷治疗前、后及20例健康对照组血清中IL-4、IL-8、IL-17和IL-22的水平。结果:慢性荨麻疹患者经18-β甘草酸苷治疗前血清中IL-4浓度(22.75±6.87pg/ml)、IL-8浓度(20.26±4.52pg/ml)、IL-17浓度(24.62±7.28pg/ml)和IL-22浓度(23.26±9.04pg/ml)高于健康对照组(P<0.05)。治疗后,IL-4浓度(14.44±4.29pg/ml)、IL-8浓度(12.24±3.32pg/ml)、IL-17浓度(13.32±1.61pg/ml)和IL-22浓度(14.32±1.59pg/ml)较治疗前显著降低(P<0.05),与健康对照比较差异无统计学意义(P>0.05)。结论:慢性荨麻疹患者的血清中存在IL-4、IL-8、IL-17和IL-22水平异于正常,提示慢性荨麻疹患者的机体免疫功能紊乱;而18-β甘草酸苷治疗后血清中IL-4、IL-8、IL-17和IL-22明显降低,提示18-β甘草酸苷可能通过影响辅助T细胞相关因子来发挥治疗慢性荨麻疹的作用。%Objective Based on measurement of chronic urticaria patients serum IL-4 and IL-8,IL-17 and IL-22 before and after 18 beta glycyrrhizin in the treatment of glycyrrhizin mechanism on treating chronic urticaria. Methods The levels of serum IL-22,IL-8,IL-17 and IL-4 in 20 cases of chronic urticaria were detected by blot Western assay and 20 cases of healthy controls. Results In patients with chronic urticaria by 18 beta glycyrrhizin treatment IL and serum concentrations of IL- 4(22.75 ± 6.87pg/ml),IL- 8 concentration(20.26 ± 4.52pg/ml),IL- 17 concentration(24.62 ± 7.28pg/ml)and IL- 22 concentration (23.26±9.04pg/ml),higher than the healthy control group(P0.05). Conclusion The serum of patients with chronic urticaria of IL-4 and IL-8,IL-17 and IL-22 levels different from normal,suggesting that chronic urticaria patients with the

  11. 社区获得性肺炎患者血清及支气管肺泡灌洗液中IL-6、IL-8和IL-10水平变化及其临床意义%The levels of IL-6,IL-8 and IL-10 in serum and bronchoalveolar lavage fluid in patients with community-acquired pneumonia and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    丁静; 魏希强; 孙伟

    2015-01-01

    目的::探讨社区获得性肺炎( CAP)患者血清和支气管肺泡灌洗液( BALF)中炎症因子白细胞介素( IL)-6、IL-8和IL-10水平的变化及其临床意义。方法:选取CAP患者50例( CAP组),入院第1天进行临床肺部感染评分,0.05);而CAP组血清中IL-8水平在入院第30天仍保持较高水平,显著高于对照组(P0. 05). The level of IL-8 in serum of CAP patients remained at a high level on day 30 of admission,which was significantly higher than that in control group(P <0. 01). Conclusions:The IL-6,IL-8 and IL-10 were involved in the pathogenesis of community-acquired pneumonia. The levels of IL-6 and IL-10 in serum and levels of IL-6,IL-8 and IL-10 in BALF can reflect the severity of pulmonary infection. The detection of IL-6,IL-8 and IL-10 in serum has certain clinical value in the early diagnosis of CAP.

  12. Clinical significance of lueasurement of changes of serum CA153、CA125、Hcy and IL-8 levels after operation in patients with Breast cancer%乳腺癌患者手术治疗前后血清CA153、CA125、Hcy和IL-8水平检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    王永东; 丁贤

    2014-01-01

    目的:探讨了乳腺癌患者手术治疗前后血清C A153、C A125、H c y和I L-8水平的变化及临床意义。方法:应用放射免疫分析法和免疫化学法对38例乳腺癌患者进行了手术治疗前后血清C A153、C A125、H c y和I L-8水平检测,并与35个正常健康人做比较。结果:乳腺癌患者在手术治疗前血清C A153、C A125、H c y和I L-8水平均非常显著地高于正常人组(P<0.05),手术治疗3个月后则与正常人比较无显著性差异(P>0.05),血清C A153水平与C A125、IL-8水平呈显著正相关(r=0.6028、0.5722、0.4986,P<0.01)结论:检测乳腺癌患者手术治疗前后血清CA153、CA125、Hcy和IL-8水平的变化对观察病情和预后判定均具有重要的临床价值。%Objective: to explore the clinical significance of changes of serum CA153、CA125、Hcy and IL-8 levels after operation in patients with Breast cancer. Methods: serum CA153、CA125、IL-8 (with RIA) serum Hcy(with immune chemistry)levels were determined in 38 patients with Breast cancer and 35 controls . Result: Before operation serum CA153、CA125、Hcy and IL-8 levels were significantly higher than those in controls (P0.05). serum CA153 levels were positively correlated with serum CA125、Hcy、IL-8 levels(r=0.6028、0.5722、0.4986,P<0.01). Conclusions:Detection of serum CA153、CA125、Hcy and IL-8 levels after operation might be of prognostic importance in patients with Breast cancer.

  13. Chemokines and chemokine receptors in mucosal homeostasis at the intestinal epithelial barrier in inflammatory bowel disease

    OpenAIRE

    Noah P Zimmerman; Vongsa, Rebecca A.; Wendt, Michael K; Michael B Dwinell

    2008-01-01

    Chemokines, a large family of small chemoattractive cytokines, and their receptors play an integral role in the regulation of the immune response and homeostasis. The ability of chemokines to attract specific populations of immune cells sets them apart from other chemoattractants. Chemokines produced within the gastrointestinal mucosa, are critical players in directing the balance between physiological and pathophysiological inflammation in health, inflammatory bowel disease and the progressi...

  14. Investigating the Effect of Endurance Training on Tumor Level of IL-8 and Serum Level of IL-17 in Female Mice with Breast Cancer

    Directory of Open Access Journals (Sweden)

    AR Kazemi

    2015-11-01

    Full Text Available Background & Objectives: Breast cancer is nowadays one of the most harmful threats to women’s health. However, exercise training plays an adjuvant role in breast cancer (Adjuvant also means preventive. So, no need to repeat preventing.. Therefore, the aim of this study is to investigate the effect of 6-week endurance training on the levels of interleukin-8 in the tumor and Interleukin-17 in the serum of mice suffering from breast cancer.  Materials & Methods: In this study, 20 female Balb/C mice were randomly divided into exercise-tumor (RET and rest-tumor (RRT groups. The mice were oriented in the environment, and one million estrogen-dependent breast cancer cells (MC4L2 were injected into the top of the right thigh of each mouse. Subsequently, the RET group performed the endurance exercise 5 days per week for 6 weeks. The tumor volume was measured by a digital caliper each week. Finally, the mice were sacrificed, and the tumor tissue was removed and kept in -70°C. Then, ELISA method was performed and the data were collected. Results: After 6 weeks of training, a significant decrease was observed in the RTE group in the serum level of IL-17 and IL-8 protein in tumor (P< 0.05. These results were consistent with the tumor growth rate. Conclusion: The findings of the present study indicate that endurance training can reduce IL-8 and IL-17 proteins in the tumor and serum of mice ill with breast cancer. Therefore, the physical activity is utilized as an important factor in the improvement of adjutant therapy along with other therapeutic methods to treat breast cancer.

  15. Molecular detection, quantification, and isolation of Streptococcus gallolyticus bacteria colonizing colorectal tumors: inflammation-driven potential of carcinogenesis via IL-1, COX-2, and IL-8

    Directory of Open Access Journals (Sweden)

    Abdulamir Ahmed S

    2010-09-01

    Full Text Available Abstract Background Colorectal cancer (CRC has long been associated with bacteremia and/or endocarditis by Streptococcus gallolyticus member bacteria (SGMB but the direct colonization of SGMB along with its molecular carcinogenic role, if any, has not been investigated. We assessed the colonization of SGMB in CRC patients with history of bacteremia (CRC-w/bac and without history of bacteremia (CRC-wo/bac by isolating SGMB from feces, mucosal surfaces of colorectum, and colorectal tissues and detecting SGMB DNA, via PCR and in situ hybridization (ISH assays targeting SodA gene in colorectal tissues. Moreover, mRNA of IL1, IL-8, COX-2, IFN-γ, c-Myc, and Bcl-2 in colorectal tissues of studied groups was assessed via ISH and RT-PCR. Results SGMB were found to be remarkably isolated in tumorous (TU and non-tumorous (NTU tissues of CRC-w/bac, 20.5% and 17.3%, and CRC-wo/bac, 12.8% and 11.5%, respectively while only 2% of control tissues revealed SGMB (P 10 CN/g respectively, showed higher colonization in TU than in NTU and in CRC-w/bac than in CRC-wo/bac (P Conclusions The current study indicated that colorectal cancer is remarkably associated with SGMB; moreover, molecular detection of SGMB in CRC was superior to link SGMB with CRC tumors highlighting a possible direct and active role of SGMB in CRC development through most probably inflammation-based sequel of tumor development or propagation via, but not limited to, IL-1, COX-2, and IL-8.

  16. Viral leads for chemokine-modulatory drugs

    DEFF Research Database (Denmark)

    Lindow, Morten; Lüttichau, Hans Rudolf; Schwartz, Thue W

    2003-01-01

    The chemokine system, which controls leukocyte trafficking, provides several potentially very attractive anti-inflammatory drug targets. However, the complexity and redundancy of this system makes it very difficult to exploit through classical drug discovery. Despite this, viruses have millions...

  17. Chemokines and chemokine receptors in mucosal homeostasis at the intestinal epithelial barrier in inflammatory bowel disease.

    Science.gov (United States)

    Zimmerman, Noah P; Vongsa, Rebecca A; Wendt, Michael K; Dwinell, Michael B

    2008-07-01

    Chemokines, a large family of small chemoattractive cytokines, and their receptors play an integral role in the regulation of the immune response and homeostasis. The ability of chemokines to attract specific populations of immune cells sets them apart from other chemoattractants. Chemokines produced within the gastrointestinal mucosa are critical players in directing the balance between physiological and pathophysiological inflammation in health, inflammatory bowel disease (IBD), and the progression to colon cancer. In addition to the well-characterized role of chemokines in directed trafficking of immune cells to the gut mucosa, the expression of chemokine receptors on the cells of the epithelium makes them active participants in the chemokine signaling network. Recent findings demonstrate an important role for chemokines and chemokine receptors in epithelial barrier repair and maintenance as well as an intricate involvement in limiting metastasis of colonic carcinoma. Increased recognition of the association between barrier defects and inflammation and the subsequent progression to cancer in IBD thus implicates chemokines as key regulators of mucosal homeostasis and disease pathogenesis. PMID:18452220

  18. Chemokine receptors in cancer metastasis and cancer cell-derived chemokines in host immune response.

    Science.gov (United States)

    Koizumi, Keiichi; Hojo, Shozo; Akashi, Takuya; Yasumoto, Kazuo; Saiki, Ikuo

    2007-11-01

    The chemotactic cytokines called chemokines are a superfamily of small secreted cytokines that were initially characterized through their ability to prompt the migration of leukocytes. Attention has been focused on the chemokine receptors expressed on cancer cells because cancer cell migration and metastasis show similarities to leukocyte trafficking. CXC chemokine receptor 4 (CXCR4) was first investigated as a chemokine receptor that is associated with lung metastasis of breast cancers. Recently, CXCR4 was reported to be a key molecule in the formation of peritoneal carcinomatosis in gastric cancer. In the present review, we highlight current knowledge about the role of CXCR4 in cancer metastases. In contrast to chemokine receptors expressed on cancer cells, little is known about the roles of cancer cell-derived chemokines. Cancer tissue consists of both cancer cells and various stromal cells, and leukocytes that infiltrate into cancer are of particular importance in cancer progression. Although colorectal cancer invasion is regulated by the chemokine CCL9-induced infiltration of immature myeloid cells into cancer, high-level expression of cancer cell-derived chemokine CXCL16 increases infiltrating CD8(+) and CD4(+) T cells into cancer tissues, and correlates with a good prognosis. We discuss the conflicting biological effects of cancer cell-derived chemokines on cancer progression, using CCL9 and CXCL16 as examples. PMID:17894551

  19. Study on the effect of serum ferritin and IL-8 in neonatal hypoxic ischemia encephalopathy%血清铁蛋白及IL-8动态检测在新生儿缺血缺氧性脑病患儿中的临床意义

    Institute of Scientific and Technical Information of China (English)

    陈艳萍; 孙雪荣; 魏涛; 高中波

    2012-01-01

    目的 探讨血清铁蛋白及白细胞介素8动态监测在缺氧缺血性脑病患儿中的作用.方法 分别检测45例HIE患儿及正常对照组30例新生健康儿出生后(48h内)及治疗5天和7天后的血清铁蛋白与白细胞白介素8水平.结果 HIE组患儿出生SF水平为(356±108) ng/ml与对照组(332±112) ng/ml比较无明显差异(P>0.05),治疗5天及7天后的SF水平分别(568±223) ng/ml,(432±169)均高于对照组SF水平(268±96) ng/ml、(226±86) ng/ml (P<0.01),HIE患儿IL-8出生及治疗5天后及7天的水平分别为(156.2±33.2)pg/ml、(135.3±22.1)pg/ml、(120.1±19.2) pg/ml与对照组(98.2±12.1)pg/ml、(96.4±11.1) pg/ml、(95.6±13.2) pg/ml比较均有显著性差异(P<0.01).结论 HIE患儿脑组织损伤后SF与IL-8水平明显升高,但IL-8的变化相对较早,因此动态检测二者含量有助于临床医生监测HIE患儿的病情,及时调整治疗方案.对患儿的早期治疗及预后有一定帮助.%Objective: To study the effect of serum ferritin and IL - 8 in neonatal hypoxic ischemia encephalopathy ( HIE ) . Methods : To measure the serum ferritin and IL - 8 levels in 45 neonates of HIE within 48h after birth and 5 and 7 days after cured. At the same time measure the serum ferritin and IL - 8 levels of 30 healthy neonates. Results: The serum ferritin level of HIE within 48 h after birth were (356 ± 108) ng/ml, and there were no significant statistical difference with healthy neonates (332 ±112) ng/ml (P > 0.05), but the serum ferritin level of HIE neonates 5 and 7 day after cured HIE (568 ±223) ng/ml, (432 ±169) ng/ml both had significant statistical difference with healthy neonates (268 ±96) ng/ml、 (226 ±86) ng/ml (P <0. 01); the IL - 8 levels of HIE within 48h after birth 5 and 7 days after cured HIE all had significant statistical differrence with healthy neonates (156. 2 ± 33. 2) pg/ml, (135.3 ±22. 1) pg/ml, (120. 1 ±19.2) pg/ml compared with (98. 2 ±12.1) pg/ml、 (96.4 ± 11. 1

  20. Trypanosoma carassii hsp70 increases expression of inflammatory cytokines and chemokines in macrophages of the goldfish (Carassius auratus L.).

    Science.gov (United States)

    Oladiran, Ayoola; Belosevic, Miodrag

    2009-10-01

    We report on the cloning and characterization of Trypanosoma carassii 70 KDa heat shock protein (hsp70). T. carassii hsp70 was secreted/excreted into culture medium in vitro and was recognized by sera from infected fish. Recombinant hsp70 (rhsp70) activated goldfish macrophages and stimulated the production of pro-inflammatory cytokines including interferon gamma (IFNgamma), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, (IL)-12 and chemokines CCL-1 and CXCL-8 (IL-8). T. carassii hsp70-induced cytokine expression was abrogated by pronase treatment of macrophages confirming the existence of receptor(s) on goldfish macrophage surface that recognize parasite molecule. Parasite hsp70 also up-regulated the expression inducible nitric oxide synthase (iNOS) isoforms A and B and induced a strong nitric oxide response of goldfish macrophages. PMID:19527750

  1. Cytokines and chemokines in respiratory secretion and severity of disease in infants with respiratory syncytial virus (RSV) infection

    DEFF Research Database (Denmark)

    Hornsleth, Allan; Loland, Lotte; Larsen, Lars B.

    2001-01-01

    Background: little is known about inflammatory mediators (IM); like cytokines, chemokines and receptors; in respiratory secretion as possible indicators of the severity of respiratory syncytial virus (RSV) disease. Nor have systematic studies been published on the ratios between IM...... as such indicators. Objective: to define the role of IM ratios as possible indicators of the severity of RSV disease. Study design: about 46 infants aged 0-9 months with acute RSV infections were studied. Prematurity (PM) and/or underlying disease (UD) were present in 11 of them. The concentrations of seven...... from 0 to 3 according to the severity of disease. Results: when 25 patients with severe disease (CS 2-3) and 21 patients with mild disease (CS 0-1) were compared with respect to different IM ratios, three ratios were related to severity of disease: IL-1/RANTES, IL-8/RANTES and TNF-R1/RANTES. When 12...

  2. Ⅲ型慢性前列腺炎患者血清IL-8、L-10、TNF-α检测的临床价值%Clinical significance of serum IL-8,IL-10 and TNF-a levels in type III chronic prostatitis

    Institute of Scientific and Technical Information of China (English)

    徐斌先; 陈卫国; 金雷; 赵读泽; 诸玲玲

    2012-01-01

    Objective To evaluate the significance of scrum Il-8,IL-10 and TNF-a levels in the diagnosis and treatment of type III chronic prostatitis (CP). Methods According to NIH classification system ,113 cases diagnosed as type III CP were classified into two groups,39 cases of type Ⅲa and 74 cases of type Ⅲb. All patients received the same treatment: combination of 0. L/d×4 W Minocin and 200 mg/d×4 W Celebrex. NIH pain symptom index (NIH-CPSI) was compared and scrum IL-8, IL-10 and TNF-a levels were measured with double antibody sandwich enzyme-linked immunocorbent assay (ELISA) before and after treatment. Results After treatment, all 113 cases showed significant decrease of NIH-CPSI (38.23 vs. 26. 38, P0. 05) ,but scrum IL-10 level was higher in type Ⅲb CP (50. 1 + 9. 3 pg/mL vs. 36. 2 + 7. 7 pg/mL,P0.05),后者IL-10水平升高更显著(50.1±9.3 pg/mL vs.36.2±7.7 pg/mL,P<0.05).结论 Ⅲ型CP存在高水平炎症反应,IL-8和TNF-a可以用于其治疗效果的评估,而IL-10的检测有助于Ⅲ型CP的分类.

  3. In vitro L.casei EPS promote small intestinal epithelial cells of Balb/c mice proliferation and secretion of IL-8, IL-10 and TGF-β%L.casei EPS体外促进Balb/c小鼠小肠上皮细胞增殖及其分泌IL-8、IL-10和TGF-β

    Institute of Scientific and Technical Information of China (English)

    霍思序; 唐彦君; 刘宁

    2013-01-01

    目的 以干酪乳杆菌(Lactobacillus casei,L.casei)胞外多糖(exopolysaccharides,EPS)为研究对象,研究其在体外对Balb/c小鼠小肠上皮细胞(small intestinal epithelial cell,IECs)增殖及其分泌IL-8、IL-10和TGF-β的影响.方法 利用嗜热菌蛋白酶消化联合差速贴壁以及免疫细胞化学鉴定的方法对Balb/c小鼠IECs进行分离和鉴定,获得实验用的IECs.用不同质量浓度的L.caseiEPS与IECs共培养,分别观察0.5、1、2h和4h后IECs的增殖情况.当用不同质量浓度的L.casei EPS处理IECs 2 h后,采用双抗体夹心ELISA法检测细胞培养上清液中细胞因子IL-8、IL-10和TGF-β的质量浓度.结果 嗜热菌蛋白酶消化联合差速贴壁的方法能够获得纯度高与活性好的IECs;L.casei EPS能够促进IECs的增殖,显著上调上清液中IL-8、IL-10和TGF-β的分泌水平(P<0.05),EPS质量浓度在0~150 μg/ml范围内呈剂量依赖关系,并且在150 μg/ml的质量浓度时达到最大值.结论 L.casei EPS能够促进IECs的增殖及IL-8、IL-10和TGF-β的分泌水平.

  4. Study on variable IL-6 and IL-8 levels in the serum of SD rats infected with Toxocara canis%感染犬弓首线虫SD大鼠血清IL-6和IL-8含量的变化

    Institute of Scientific and Technical Information of China (English)

    程云; 李建华; 彭景贤

    2010-01-01

    目的 通过检测白细胞介素-6(IL-6)、白细胞介素-8(IL-8)的含量,在免疫分子水平上探讨大鼠感染犬弓首线 虫后免疫功能的变化. 方法 将80只大鼠随机分为两组,每组40只,实验组每只大鼠灌胃犬弓首线虫感染期虫卵约3 000个(对照组大鼠灌胃生理盐水).分别于大鼠感染犬弓首线虫后第1、2、3、4、5周随机取实验组和对照组大鼠各8只,常规股动脉取血,分离血清,用放射免疫法测定IL-6、IL-8含量. 结果 ①实验组IL-6含量在第1、2、3、4、5周均高于对照组(P<0.05或P<0.01),第2周达最高值,之后下降;②实验组IL-8含量在第1、2、3、5周高于对照组(P<0.05或P<0.01),第4周与对照组比较差异无统计学意义(P>0.05). 结论 SD大鼠感染犬弓首线虫后血清IL-6含量升高,提示IL-6与抗虫作用有关,但随着时间的推移,这种保护作用逐渐减弱;感染鼠血清趋化性细胞因子IL-8含量升高,且观察期内含量变化不大,提示非特异性免疫功能增强,且在移行期非特异性免疫功能无显著变化.

  5. IL-17、IL-6、IL-8在子痫前期孕妇血清及胎盘组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    吴海英

    2013-01-01

    目的:研究子痫前期孕妇血清及胎盘组织中IL-17、IL-6、IL-8表达方式和意义。方法将本院2012-2013年子痫前期孕妇30例设为观察组,另选同期正常孕妇30例设为对照组。酶联免疫吸附法(ELISA)检测两组孕妇血清中IL-17、IL-6、IL-8,免疫组化法检测胎盘中IL-17、IL-6、IL-8的表达水平。结果观察组血清IL-17、IL-6、IL-8高于对照组、组织胎盘IL-6指数低于对照组(P0.05)。结论炎性细胞因子IL-17、IL-6、IL-8和子痫前期之间存在明显联系,是临床诊断子痫前期孕妇的重要指数,值得重视。

  6. Multiplex cytokine analyses in dogs with pyometra suggest involvement of KC-like chemokine in canine bacterial sepsis.

    Science.gov (United States)

    Karlsson, Iulia; Hagman, Ragnvi; Johannisson, Anders; Wang, Liya; Södersten, Fredrik; Wernersson, Sara

    2016-02-01

    Clinical diagnostic criteria for sepsis (systemic inflammatory response syndrome caused by infection) are unspecific and, therefore, biomarkers for sepsis diagnosis are needed for appropriate treatment and patient survival. Pyometra, a common disease caused by bacterial infection of the uterus, results in sepsis in nearly 60% of cases in dogs. We used dogs with pyometra as a natural model for sepsis and collected serum samples from 39 dogs, of which 22 with pyometra and 17 healthy controls. Dogs with pyometra were further grouped into dogs with sepsis (n=18) and without sepsis (n=4). Serum concentrations of a panel of cytokines, including keratinocyte-derived chemokine (KC)-like, granulocyte-macrophages colony stimulating factor (GM-CSF), interleukin (IL)-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, chemokine C-X-C motif ligand (CXCL)10 and tumor necrosis factor (TNF)-α, were measured using multiplex analyses. Serum C-reactive protein (CRP) levels were determined using an automated immunoturbidimetric assay. In addition to physical examination hematological and serum biochemical analyses were performed to evaluate the overall status of the dogs. Significantly higher concentrations of KC-like (757 vs 304 pg/ml) were detected in dogs with pyometra as compared to healthy dogs. Within the pyometra group, dogs with sepsis compared to dogs without sepsis had a higher KC-like concentration (873 vs 300 pg/ml). Hemoglobin levels were significantly lower in dogs with pyometra compared to healthy dogs, regardless of the presence or absence of sepsis, and correlated negatively with KC-like. KC-like concentrations correlated positively with CRP, number of hospitalization days, number of monocytes, concentrations of IL-8, and percentage band neutrophils. Our data suggest that bacterial infection triggers the expression of KC-like and further studies are warranted of KC-like as a possible biomarker for diagnosing sepsis and uterine bacterial infection in dogs. PMID:26837616

  7. Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Tani, M; Jensen, J;

    1999-01-01

    Chemokines direct tissue invasion by specific leukocyte populations. Thus, chemokines may play a role in multiple sclerosis (MS), an idiopathic disorder in which the central nervous system (CNS) inflammatory reaction is largely restricted to mononuclear phagocytes and T cells. We asked whether...

  8. Induction of TLR-2 and TLR-5 expression by Helicobacter pylori switches cagPAI-dependent signalling leading to the secretion of IL-8 and TNF-α.

    Directory of Open Access Journals (Sweden)

    Suneesh Kumar Pachathundikandi

    Full Text Available Helicobacter pylori is the causative agent for developing gastritis, gastric ulcer, and even gastric cancer. Virulent strains carry the cag pathogenicity island (cagPAI encoding a type-IV secretion system (T4SS for injecting the CagA protein. However, mechanisms of sensing this pathogen through Toll-like receptors (TLRs and downstream signalling pathways in the development of different pathologies are widely unclear. Here, we explored the involvement of TLR-2 and TLR-5 in THP-1 cells and HEK293 cell lines (stably transfected with TLR-2 or TLR-5 during infection with wild-type H. pylori and isogenic cagPAI mutants. H. pylori triggered enhanced TLR-2 and TLR-5 expression in THP-1, HEK293-TLR2 and HEK293-TLR5 cells, but not in the HEK293 control. In addition, IL-8 and TNF-α cytokine secretion in THP-1 cells was induced in a cagPAI-dependent manner. Furthermore, we show that HEK293 cells are not competent for the uptake of T4SS-delivered CagA, and are therefore ideally suited for studying TLR signalling in the absence of T4SS functions. HEK293 control cells, which do not induce TLR-2 and TLR-5 expression during infection, only secreted cytokines in small amounts, in agreement with T4SS functions being absent. In contrast, HEK293-TLR2 and HEK293-TLR5 cells were highly competent for inducing the secretion of IL-8 and TNF-α cytokines in a cagPAI-independent manner, suggesting that the expression of TLR-2 or TLR-5 has profoundly changed the capability to trigger pro-inflammatory signalling upon infection. Using phospho-specific antibodies and luciferase reporter assays, we further demonstrate that H. pylori induces IRAK-1 and IκB phosphorylation in a TLR-dependent manner, and this was required for activation of transcription factor NF-κB. Finally, NF-κB activation in HEK293-TLR2 and HEK293-TLR5 cells was confirmed by expressing p65-GFP which was translocated from the cytoplasm into the nucleus. These data indicate that H. pylori-induced expression

  9. Overexpression of S100A7 protects LPS-induced mitochondrial dysfunction and stimulates IL-6 and IL-8 in HaCaT cells.

    Directory of Open Access Journals (Sweden)

    Wenyan Sun

    Full Text Available S100A7 (or psoriasin is distributed in the cytoplasm of keratinocytes of normal human epidermis, and it is overexpressed in many epidermal inflammatory diseases. Lipopolysaccharide (LPS induces mitochondrial function changes, which play important roles in multiple cellular mechanisms including inflammation. Although S100A7 expression is regulated by various factors in the human epidermis during inflammation, whether S100A7 interacts with mitochondria in keratinocytes is not clear.Our study was designed to investigate whether S100A7 could prohibit mitochondrial dysfunction and stimulate cytokines in cultured normal HaCaT cells treated with LPS.We generated HaCaT cells that constitutively express enhanced green fluorescence protein (EGFP-S100A7 (S100A7-EGFP or EGFP alone, as a control. Here, we show that S100A7-EGFP HaCaT cells exhibit an increase in mitochondrial DNA (mtDNA copy number and mitochondrial membrane potential (MMP. qRT-PCR revealed that expression of three main mitochondrial biogenesis-associated genes was significantly increased: PPAR-coactivator-1alpha (PGC-1α, the mitochondrial transcription factor A (Tfam and nuclear respiratory factor-1 (NRF1. S100A7 overexpression increased mtDNA content and effectively increased intracellular adenosine 5'-triphosphate (ATP production, while decreasing reactive oxygen species (ROS generation. S100A7 overexpression also significantly decreased the expression of Mfn2 and increased DRP1 expression compared with control EGFP cells. S100A7 down-regulated the expression of the autophagy-related proteins Beclin-1 and LC3B. S100A7 also increased expression of IL-6 and IL-8 cytokines. Knockdown of S100A7 decreased MMP and disrupted mitochondrial homeostasis.These findings demonstrate that S100A7 stimulates mitochondrial biogenesis and increases mitochondrial function in HaCaT cells treated with LPS; and S100A7 also promotes secretion of IL-6 and IL-8.

  10. 慢性乙型肝炎和肝功能衰竭患者血清IL-32、IL-6、IL-8检测的意义

    Institute of Scientific and Technical Information of China (English)

    陈海芬

    2015-01-01

    目的 探讨血清白细胞介素(IL)-32、IL-6及IL-8检测在慢性乙型肝炎和肝功能衰竭中的意义.方法 分别选取慢性乙型肝炎患者(130例)、肝功能衰竭患者(40例)和健康对照者(60例),比较3组间和不同病情严重程度的乙型肝炎患者间的IL-32、IL-6和IL-8水平.结果 肝炎组和肝衰竭组的IL-32、IL-8及IL-6均高于对照组(均P< 0.05),肝衰竭组的IL-32、IL-8及IL-6均高于肝炎组(均P<0.05);且病情越严重,IL-32、IL-8及IL-6值越高(均P< 0.05).结论 IL-32、IL-8及IL-6细胞因子的水平会随着病情严重程度的增加而增加,可以用于判断病情的严重程度,对病情加以评估,有重要的临床意义.

  11. Autocrine Acetylcholine, Induced by IL-17A via NFκB and ERK1/2 Pathway Activation, Promotes MUC5AC and IL-8 Synthesis in Bronchial Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Angela Marina Montalbano

    2016-01-01

    Full Text Available IL-17A is overexpressed in the lung during acute neutrophilic inflammation. Acetylcholine (ACh increases IL-8 and Muc5AC production in airway epithelial cells. We aimed to characterize the involvement of nonneuronal components of cholinergic system on IL-8 and Muc5AC production in bronchial epithelial cells stimulated with IL-17A. Bronchial epithelial cells were stimulated with recombinant human IL-17A (rhIL-17A to evaluate the ChAT expression, the ACh binding and production, the IL-8 release, and the Muc5AC production. Furthermore, the effectiveness of PD098,059 (inhibitor of MAPKK activation, Bay11-7082 (inhibitor of IkBα phosphorylation, Hemicholinium-3 (HCh-3 (choline uptake blocker, and Tiotropium bromide (Spiriva® (anticholinergic drug was tested in our in vitro model. We showed that rhIL-17A increased the expression of ChAT, the levels of ACh binding and production, and the IL-8 and Muc5AC production in stimulated bronchial epithelial cells compared with untreated cells. The pretreatment of the cells with PD098,059 and Bay11-7082 decreased the ChAT expression and the ACh production/binding, while HCh-3 and Tiotropium decreased the IL-8 and Muc5AC synthesis in bronchial epithelial cells stimulated with rhIL-17A. IL-17A is involved in the IL-8 and Muc5AC production promoting, via NFκB and ERK1/2 pathway activation, the synthesis of ChAT, and the related activity of autocrine ACh in bronchial epithelial cells.

  12. APE1/Ref-1 siRNA inhibits IL-6 and IL-8 secretion by cultured bone marrow stromal cells isolated from multiple myeloma patients%APE1/Ref-1 siRNA抑制多发性骨髓瘤骨髓基质细胞IL-6及IL-8分泌的体外研究

    Institute of Scientific and Technical Information of China (English)

    谢家印; 王阁; 王东; 李梦侠; 向德兵; 杨镇洲; 杨宇馨; 李增鹏; 曾林立; 仲召阳

    2009-01-01

    目的 体外通过APE1/Ref-1 siRNA敲低多发性骨髓瘤骨髓基质细胞(bone marrow stromal cells,BMSCs)APE1/Ref-1的表达,观察BMSCs的增殖及分泌细胞因子IL-6、IL-8的变化,初步探讨BMSCs APE1/Ref-1表达的功能特点.方法 通过免疫细胞化学染色法定量榆测35例初治、11例复发/难治多发性骨髓瘤患者及10例正常人BMSCsAPE1/Ref-1的表达特点及其差异,经Adv5-APE1/Ref-1 siRNA感染BMSCs后,流式细胞仪检测BMSCs细胞周期的变化;ELISA法检测BMSCs分泌IL-6、IL-8的水平变化情况.结果 多发性骨髓瘤BMSCs的APE1/Ref-1蛋白阳性表达率显著高于正常BMSCs APE1/Ref-1蛋白阳性表达率(P<0.05),且多发性骨髓瘤BMSCs的APE1/Ref-1呈细胞核及核浆共间表达方式.Adv5-APE1/Ref-1 siRNA感染敲低多发性骨髓瘤及正常BMSCs APE1/Ref-1的表达量呈进行性减少(P<0.01),同时发现APE1/Ref-1 siRNA对多发性骨髓瘤BMSCs抑制作用更明显.Adv5-APE1/Ref-1 siRNA感染BMSCs后对正常人及骨髓瘤患者BMSCs分泌细胞因子IL-6、IL-8的量有显著的抑制作用,特别是感染72 h后,骨髓瘤患者及正常人的BMSCs分泌IL-6[初治患者(246.29±46.51)pg/ml,复发/难治患者(365.09±75.25)pg/ml]、IL-8[初治患者(118.77±18.08)pg/ml,复发/难治患者(188.71±33.76)pg/ml]的量最低,与其他时段比较差异有统计学意义(P<0.01).结论 多发性骨髓瘤BMscs APE1/Ref-1的表达特点不同于正常BMSCs,可能导致其功能差异;APE1/Ref-1 siRNA敲低了MM BMSCsAPE1/Ref-1的表达,同时明显抑制了其IL-6、IL-8的分泌,减少了对骨髓瘤细胞的促增殖和凋亡作用.

  13. Synergistic cooperation between methamphetamine and HIV-1 gsp120 through the P13K/Akt pathway induces IL-6 but not IL-8 expression in astrocytes.

    Directory of Open Access Journals (Sweden)

    Ankit Shah

    Full Text Available HIV-1 envelope protein gp120 has been extensively studied for neurotoxic effects that have been attributed to the increased expression of various proinflammatory cytokines in the CNS. Recently we have shown that methamphetamine (MA also increases expression of proinflammatory cytokines in astrocytes. However, combined effect of gp120 and MA is not known. The present study was undertaken to determine cumulative effect and the mechanism(s/pathways involved in the functional interaction between gp120 and MA in SVGA astrocytes. Our results clearly suggest that gp120 and MA affect IL-6 but not IL-8 in a synergistic manner and this synergy was mediated by PI3K/Akt and NF-κB pathways. Inhibition of either of these pathways could abrogate the increased expression of IL-6 due to MA or gp120 alone, as well as the increased expression of IL-6 when the astrocytes were treated with both gp120 and MA. These results were confirmed by both, using chemical inhibitors/siRNA as well as western blotting. This study therefore provides novel information regarding the interaction between MA and gp120 in terms of the expression of IL-6 and the mechanisms underlying potential synergy between MA and gp120 in astrocytes.

  14. Adh enhances Actinobacillus pleuropneumoniae pathogenicity by binding to OR5M11 and activating p38 which induces apoptosis of PAMs and IL-8 release.

    Science.gov (United States)

    Wang, Lei; Qin, Wanhai; Zhang, Jing; Bao, Chuntong; Zhang, Hu; Che, Yanyi; Sun, Changjiang; Gu, Jingmin; Feng, Xin; Du, Chongtao; Han, Wenyu; Richard, Paul Langford; Lei, Liancheng

    2016-04-05

    Members of the Trimeric Autotransporter Adhesin (TAA) family play a crucial role in the adhesion of Gram-negative pathogens to host cells, but the immunopathogenesis of TAAs remains unknown. Our previous studies demonstrated that Adh from Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is required for full bacterial pathogenicity. Alveolar macrophages are the first line of defense against respiratory infections. This study compared the interactions between porcine alveolar macrophages (PAMs) and wild-type A. pleuropneumoniae (5b WT) or an Adh-deletion strain (5b ΔAdh) via gene microarray, immunoprecipitation and other technologies. We found that Adh was shown to interact with the PAMs membrane protein OR5M11, an olfactory receptor, resulting in the high-level secretion of IL-8 by activation of p38 MAPK signaling pathway. Subsequently, PAMs apoptosis via the activation of the Fax and Bax signaling pathways was observed, followed by activation of caspases 8, 9, and 3. The immunological pathogenic roles of Adh were also confirmed in both murine and piglets infectious models in vivo. These results identify a novel immunological strategy for TAAs to boost the pathogenicity of A. pleuropneumoniae. Together, these datas reveal the high versatility of the Adh protein as a virulence factor and provide novel insight into the immunological pathogenic role of TAAs.

  15. Autophagy Mediates HBx-Induced Nuclear Factor-κB Activation and Release of IL-6, IL-8, and CXCL2 in Hepatocytes.

    Science.gov (United States)

    Luo, Millore X M; Wong, Sunny H; Chan, Matthew T V; Yu, Le; Yu, Sidney S B; Wu, Feng; Xiao, Zhangang; Wang, Xiaojuan; Zhang, Lin; Cheng, Alfred S L; Ng, Simon S M; Chan, Francis K L; Cho, Chi H; Yu, Jun; Sung, Joseph J Y; Wu, William K K

    2015-10-01

    Hepatitis B virus (HBV) and one of its encoded proteins, HBV X protein (HBx), have been shown to induce autophagy in hepatoma cells. Substantial evidence indicates that autophagy is a potent suppressor of inflammation. However, sporadic reports suggest that autophagy could promote pro-inflammatory cytokine expression and inflammation in some biological contexts. Here, we show that overexpression of HBx induces LC3B-positive autophagosome formation, increases autophagic flux and enhances the expression of ATG5, ATG7, and LC3B-II in normal hepatocytes. Abrogation of autophagy by small interfering RNA against ATG5 and ATG7 prevents HBx-induced formation of autophagosomes. Autophagy inhibition also abrogates HBx-induced activation of nuclear factor-κB (NF-κB) and production of interleukin-6 (IL-6), IL-8, and CXCL2. These findings suggest that autophagy is required for HBx-induced NF-κB activation and pro-inflammatory cytokine production and could shed new light on the complex role of autophagy in the modulation of inflammation.

  16. 血清CA15-3、CA50、CA19-9和IL-8检测对女性乳腺癌的诊断价值

    Institute of Scientific and Technical Information of China (English)

    高永旺; 蒋炳辰

    2014-01-01

    Objective:To investigate the clinical signficance of differences on serum CA15-3,CA50,CA19-9,IL-8 levels detection in patients with breast cancer. Methods:Serum CA15-3,CA50,CA19-9,IL-8 concentration from 34 patients (female) with breast cancer and 34 healthy normal controls (female) were determined by RIA and CLIA. Results:The serum CA15-3,CA50,IL-8 levels in patients with breast cancer were significant higher than those in controls. But the serum CA19-9 levels were no significant difference from those in controls.Conclusion:Detection of serum CA15-3,CA50,IL-8 levels might be of prognostic importance in patients with breast cancer.%目的:探讨血清CA15-3、CA50、CA19-9和IL-8检测对乳腺癌患者诊断的临床意义。方法:应用放射免疫法和化学发光法对34例乳腺癌患者(均为女性)进行血清的CA15-3、CA50、CA19-9和IL-8检测,并与34名正常人(均为女性)进行相关对比分析。结果:乳腺癌患者的CA15-3、CA50和IL-8含量水平明显高于对照组(P<0.05),而CA19-9与正常人对照组无明显差异(P>0.05)。结论:血清CA15-3、CA50和IL-8的检测对乳腺癌的发病、预防、诊断和治疗均有重要的临床价值。

  17. Fulminant lymphocytic choriomeningitis virus-induced inflammation of the CNS involves a cytokine-chemokine-cytokine-chemokine cascade

    DEFF Research Database (Denmark)

    Christensen, Jeanette E; Simonsen, Stine; Fenger, Christina;

    2009-01-01

    Intracerebral inoculation of immunocompetent mice with lymphocytic choriomeningitis virus (LCMV) normally results in fatal CD8+ T cell mediated meningoencephalitis. However, in CXCL10-deficient mice, the virus-induced CD8+ T cell accumulation in the neural parenchyma is impaired, and only 30...... of the CNS, and astrocytes are the dominant expressors in the neural parenchyma, not microglial cells or recruited bone marrow-derived cell types. These results are consistent with a model suggesting a bidirectional interplay between resident cells of the CNS and the recruited virus-specific T cells...

  18. Chemokines in CSF of Alzheimer's disease patients

    Directory of Open Access Journals (Sweden)

    Jôice Dias Corrêa

    2011-06-01

    Full Text Available Some studies have linked the presence of chemokines to the early stages of Alzheimer's disease (AD. Then, the identification of these mediators may contribute to diagnosis. Our objective was to evaluate the levels of beta-amyloid (BA, tau, phospho-tau (p-tau and chemokines (CCL2, CXCL8 and CXCL10 in the cerebrospinal fluid (CSF of patients with AD and healthy controls. The correlation of these markers with clinical parameters was also evaluated. The levels of p-tau were higher in AD compared to controls, while the tau/p-tau ratio was decreased. The expression of CCL2 was increased in AD. A positive correlation was observed between BA levels and all chemokines studied, and between CCL2 and p-tau levels. Our results suggest that levels of CCL2 in CSF are involved in the pathogenesis of AD and it may be an additional useful biomarker for monitoring disease progression.

  19. Chemokines and chemokine receptors expression in the lesions of patients with American cutaneous leishmaniasis

    Directory of Open Access Journals (Sweden)

    Nilka Luisa Diaz

    2013-06-01

    Full Text Available American cutaneous leishmaniasis (ACL presents distinct active clinical forms with different grades of severity, known as localised (LCL, intermediate (ICL and diffuse (DCL cutaneous leishmaniasis. LCL and DCL are associated with a polarised T-helper (Th1 and Th2 immune response, respectively, whereas ICL, or chronic cutaneous leishmaniasis, is associated with an exacerbated immune response and a mixed cytokine expression profile. Chemokines and chemokine receptors are involved in cellular migration and are critical in the inflammatory response. Therefore, we evaluated the expression of the chemokines CXCL10, CCL4, CCL8, CCL11 and CXCL8 and the chemokine receptors CCR3, CXCR3, CCR5 and CCR7 in the lesions of patients with different clinical forms of ACL using immunohistochemistry. LCL patients exhibited a high density of CXCL10+, CCL4+ and CCL8+ cells, indicating an important role for these chemokines in the local Th1 immune response and the migration of CXCR3+ cells. LCL patients showed a higher density of CCR7+ cells than ICL or DCL patients, suggesting major dendritic cell (DC migration to lymph nodes. Furthermore, DCL was associated with low expression levels of Th1-associated chemokines and CCL11+ epidermal DCs, which contribute to the recruitment of CCR3+ cells. Our findings also suggest an important role for epidermal cells in the induction of skin immune responses through the production of chemokines, such as CXCL10, by keratinocytes.

  20. Expression and clinical significance of serum interleukin-8 level in patients with oral squamous cell carcinoma%口腔鳞状细胞癌患者血清IL-8的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    顾文莉; 杨佳佳

    2011-01-01

    PURPOSE: To explore the clinical significance of serum interleukin-8 (IL-8) level in patients with oral squamous cell carcinoma (OSCC). METHODS: Twenty-seven serum specimens pathologically confirmed as OSCC were tested, 10 healthy serum specimens were used as control. The expression of serum IL-8 was measured by ELISA.Data was presented as mean ± standard error. Statistical analysis was performed by SPSS 13.0 software package and two-tailed independent sample t test was used to determine the difference between the two groups. RESULTS: The level of serum IL-8 in OSCC patients was significantly higher than that in the control (P<0.01). The high expression of IL-8 correlated with clinical pathologic stage(P<0.01) and lymph node metastasis (P<0.05). CONCLUSIONS: The expression of serum IL-8 correlates significantly with the biological behavior of OSCC, and it can be used as a prognostic molecular marker for OSCC. Supported by the Third Session of Excellent Youth Foundation of Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine.%目的:观察免疫趋化因子白细胞介素8(IL-8)在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)患者血清中的表达,探讨其与OSCC临床病理因素的相关性.方法:应用酶联免疫反应(enzyme-linked immunosorbent assay,ELISA)测定27例处于不同临床分期的OSCC患者和10例健康体检者血清中的IL-8水平.检测结果以-x±s表示,应用SPSS 13.0软件包对数据进行t检验.结果:OSCC肿瘤组患者血清IL-8水平显著高于对照组(P<0.01),临床Ⅲ、Ⅳ期OSCC患者血清IL-8水平显著高于Ⅰ、Ⅱ期患者(P<0.01);有颈淋巴结转移的OSCC患者,血清IL-8水平显著高于无转移者(P<0.01).结论:血清IL-8水平与口腔鳞状细胞癌的病理分级、临床分期及淋巴结转移等密切相关,是一种具有应用潜力的OSCC临床检测指标.

  1. 宫颈癌患者外周血中IL-6、IL-8和IL-17的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    姜波

    2015-01-01

    目的:探讨宫颈癌患者外周血中IL-6、IL-8和IL-17的表达及临床意义.方法:选择2011年1月至2012年12月期间50例宫颈癌患者为研究对象,按照临床分期分为Ⅰ期(16例)、Ⅱ期(24例)和Ⅲ期(10例).另选择CIN患者50例作为CIN组,选择健康女性50例为对照组.统计受试者血清IL-6、IL-8和IL-17水平,并对血清IL-6、IL-8和IL-17表达与年龄、宫颈癌病程、临床分期、高危型人乳头瘤病毒(HR-HPV)感染、BMI进行相关性分析.结果:宫颈癌组血清IL-6、IL-8和IL-17水平高于CIN组和对照组,差异有统计学意义(P<0.01),CIN组血清IL-6、IL-8和IL-17水平高于对照组,差异有统计学意义(P<0.01);随着宫颈癌临床分期的增加,IL-6、IL-8和IL-17的表达呈增强趋势,且3组间两两比较差异均有统计学意义(P<0.01);HR-HPV阳性组血清IL-6、IL-8和IL-17水平高于HR-HPV阴性组,差异有统计学意义(P<0.01);血清IL-6、IL-8和1L-17表达与宫颈癌临床分期、HR-HPV感染均呈正相关(P<0.05),血清IL-6、IL-8和IL-17表达之间均呈正相关(P<0.05).结论:宫颈癌患者血清中IL-6、IL-8和IL-17呈高表达,宫颈癌中IL-6、IL-8和IL-17的表达与宫颈癌的发生、进展及HR-HPV感染密切相关.

  2. Chemokine signaling involving chemokine (C-C motif) ligand 2 plays a role in descending pain facilitation

    Institute of Scientific and Technical Information of China (English)

    Wei Guo; Hu Wang; Shiping Zou; Ronald Dubner; Ke Ren

    2012-01-01

    Objective Despite accumulating evidence on a role of immune cells and their associated chemicals in mechanisms of pain,few studies have addressed the potential role of chemokines in the descending facilitation of persistent pain.The present study was undertaken to test the hypothesis that the chemokine (C-C motif) ligand 2 (CCL2) (commonly known as monocyte chemoattractant protein-1) signaling in the rostral ventromedial medulla (RVM),a pivotal structure in brainstem pain modulatory circuitry,is involved in descending pain facilitation in rats.Methods An L5 spinal nerve ligation (SNL) was produced in rats under pentobarbital anesthesia.Western blot and immunohistochemistry were used to detect the expression levels of CCL2 and CCL2 receptor (CCR2),and examine their distributions compared with the neuronal marker NeuN as well as glial markers glial fibrillary acidic protein (GFAP,astroglial) and CD11b (microglial),respectively.Results SNL induced an increase in CCL2 expression in the RVM,and this returned to the control level at 4 weeks after injury.The induced CCL2 colocalized with NeuN,but not with GFAP and CD11b.CCR2 was also upregulated by SNL in the RVM,and this increase lasted for at least 4 weeks.CCR2 was colocalized with CD1 1b but not GFAP.Few RVM neurons also exhibited CCR2 staining.Neutralizing CCL2 with an anti-CCL2 antibody (0.2-20 ng) or injecting RS-102895 (0.1-10 pmol),a CCR2b chemokine receptor antagonist,into the RVM on day 1 after SNL,significantly attenuated the established thermal and mechanical hypersensitivity.In addition,injection of recombinant rat CCL2 (0.03-3pmol) into the RVM induced dose-dependent hyperalgesia,which was prevented by pretreatment with RS-102895 (10pmol).Interleukin-1β (IL-1β),a potent inducer of neuronal CCL2,was also selectively upregulated in RVM reactive astrocytes.Injection of IL-1β (120 fmol) into the RVM induced behavioral hyperalgesia,which was blocked by RS-102895(10 pmol).However,an IL-1 receptor antagonist (3

  3. Chemokines and Chemokine Receptors: Their Manifold Roles in Homeostasis and Disease

    Institute of Scientific and Technical Information of China (English)

    Yingying Le; Ye Zhou; Pablo Iribarren; Ji Ming Wang

    2004-01-01

    Chemokines are a superfamily of small proteins that bind to G protein-coupled receptors on target cells and were originally discovered as mediators of directional migration of immune cells to sites of inflammation and injury. In recent years, it has become clear that the function of chemokines extends well beyond the role in leukocyte chemotaxis. They participate in organ development, angiogenesis/angiostasis, leukocyte trafficking and homing, tumorigenesis and metastasis, as well as in immune responses to microbial infection. Therefore,chemokines and their receptors are important targets for modulation of host responses in pathophysiological conditions and for therapeutic intervention of human diseases.

  4. Chemokines and Chemokine Receptors: Their Manifold Roles in Homeostasis and Disease

    Institute of Scientific and Technical Information of China (English)

    YingyingLe; YeZhou; PabloIribarren; JiMingWang

    2004-01-01

    Chemokines are a superfamily of small proteins that bind to G protein-coupled receptors on target cells and were originally discovered as mediators of directional migration of immune cells to sites of inflammation and injury. In recent years, it has become clear that the function of chemokines extends well beyond the role in leukocyte chemotaxis. They participate in organ development, angiogenesis/angiostasis, leukocyte trafficking and homing, tumorigenesis and metastasis, as well as in immune responses to microbial infection. Therefore, chemokines and their receptors are important targets for modulation of host responses in pathophysiological conditions and for therapeutic intervention of human diseases. Cellular & Molecular Immunology. 2004;1(2):95-104.

  5. Circulating cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia determined by multiplex suspension array

    Directory of Open Access Journals (Sweden)

    Bekő Gabriella

    2010-12-01

    Full Text Available Abstract Background Preeclampsia is a severe complication of pregnancy characterized by an excessive maternal systemic inflammatory response with activation of both the innate and adaptive arms of the immune system. Cytokines, chemokines and adhesion molecules are central to innate and adaptive immune processes. The purpose of this study was to determine circulating levels of cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia in a comprehensive manner, and to investigate their relationship to the clinical features and laboratory parameters of the study participants, including markers of overall inflammation (C-reactive protein, endothelial activation (von Willebrand factor antigen and endothelial injury (fibronectin, oxidative stress (malondialdehyde and trophoblast debris (cell-free fetal DNA. Results Serum levels of interleukin (IL-1beta, IL-1 receptor antagonist (IL-1ra, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-18, interferon (IFN-gamma, tumor necrosis factor (TNF-alpha, transforming growth factor (TGF-beta1, interferon-gamma-inducible protein (IP-10, monocyte chemotactic protein (MCP-1, intercellular adhesion molecule (ICAM-1 and vascular cell adhesion molecule (VCAM-1 were measured in 60 preeclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women by multiplex suspension array and ELISA. In normal pregnancy, the relative abundance of circulating IL-18 over IL-12p70 and the relative deficiency of the bioactive IL-12p70 in relation to IL-12p40 might favour Th2-type immunity. Although decreased IL-1ra, TNF-alpha and MCP-1 concentrations of healthy pregnant relative to non-pregnant women reflect anti-inflammatory changes in circulating cytokine profile, their decreased serum IL-10 and increased IP-10 levels might drive pro-inflammatory responses. In addition to a shift towards Th1-type immunity (expressed by the increased IL-2/IL-4 and IFN-gamma/IL-4 ratios, circulating levels of

  6. Roles of Chemokines in Thymopoiesis: Redundancy and Regulation

    Institute of Scientific and Technical Information of China (English)

    Wenxian Fu; Weifeng Chen

    2004-01-01

    Thymus is the primary lymphoid organ involved in the development of thymocytes. Maturation related events of thymocytes within thymus, especially the widely discussed directional migration of thymocytes, is regulated by chemokines via chemokine receptors mediated signaling pathway. Multiple types of chemokines and chemokine receptors, as components of the network-interaction within thymic microenvironment, are involved in the thymopoiesis. It appears that these chemokines are functionally redundant and such phenomenon may be explained not only by the promiscuous, non-one-to-one matching between ligands-receptors within CXC or CC chemokine subfamily, but also by the various spatio-temporal expression patterns within different cell types and developmental stages. The redundancy and regulation of thymus expressed chemokines and chemokine receptors during thymocyte development are herein discussed.

  7. Roles of Chemokines in Thymopoiesis: Redundancy and Regulation

    Institute of Scientific and Technical Information of China (English)

    WenxianFu; WeifengChen

    2004-01-01

    Thymus is the primary lymphoid organ involved in the development of thymocytes. Maturation related events of thymocytes within thymus, especially the widely discussed directional migration of thymocytes, is regulated by chemokines via chemokine receptors mediated signaling pathway. Multiple types of chemokines and chemokine receptors, as components of the network-interaction within thymic microenvironment, are involved in the thymopoiesis. It appears that these chemokines are functionally redundant and such phenomenon may be explained not only by the promiscuous, non-one-to-one matching between ligands-receptors within CXC or CC chemokine subfamily, but also by the various spatio-temporal expression patterns within different cell types and developmental stages. The redundancy and regulation of thymus expressed chemokines and chemokine receptors during thymocyte development are herein discussed. Cellular & Molecular Immunology.

  8. Neuronal Chemokines: Versatile Messengers In Central Nervous System Cell Interaction

    OpenAIRE

    de Haas, A. H.; van Weering, H. R. J.; Jong, E.K.; Boddeke, H. W. G. M.; Biber, K.P.H.

    2007-01-01

    Whereas chemokines are well known for their ability to induce cell migration, only recently it became evident that chemokines also control a variety of other cell functions and are versatile messengers in the interaction between a diversity of cell types. In the central nervous system (CNS), chemokines are generally found under both physiological and pathological conditions. Whereas many reports describe chemokine expression in astrocytes and microglia and their role in the migration of leuko...

  9. Cytokine and Chemokine Profile in Amicrobial Pustulosis of the Folds: Evidence for Autoinflammation.

    Science.gov (United States)

    Marzano, Angelo V; Tavecchio, Simona; Berti, Emilio; Gelmetti, Carlo; Cugno, Massimo

    2015-12-01

    Autoinflammation has recently been suggested in the pathogenesis of neutrophilic dermatoses but systematic studies on their cytokine profile are lacking. Notably, amicrobial pustulosis of the folds (APF), classified among neutrophilic dermatoses, has been studied only in small case series. In our University Hospital, we conducted an observational study on 15 APF patients, analyzing their clinical and laboratory features with a follow-up of 9 months to 20 years. Skin cytokine pattern of 9 of them was compared to that of 6 normal controls. In all patients, primary lesions were pustules symmetrically involving the skin folds and anogenital region with a chronic-relapsing course and responding to corticosteroids. Dapsone, cyclosporine, and tumor necrosis factor blockers were effective in refractory cases. In skin samples, the expressions of interleukin (IL)-1β, pivotal cytokine in autoinflammation, and its receptors I and II were significantly higher in APF (P = 0.005, 0.018, and 0.034, respectively) than in controls. Chemokines responsible for neutrophil recruitment such as IL-8 (P = 0.003), CXCL 1/2/3 (C-X-C motif ligand 1/2/3) (P = 0.010), CXCL 16 (P = 0.045), and RANTES (regulated on activation, normal T cell expressed and secreted) (P = 0.034) were overexpressed. Molecules involved in tissue damage like matrix metalloproteinase-2 (MMP-2) (P = 0.010) and MMP-9 (P = 0.003) were increased. APF is a pustular neutrophilic dermatosis with a typical distribution in all patients. The disorder may coexist with an underlying autoimmune/dysimmune disease but is often associated only with a few autoantibodies without a clear autoimmunity. The overexpression of cytokines/chemokines and molecules amplifying the inflammatory network supports the view that APF has an important autoinflammatory component. PMID:26683967

  10. Cytokine, chemokine, and growth factor profile of platelet-rich plasma.

    Science.gov (United States)

    Mussano, F; Genova, T; Munaron, L; Petrillo, S; Erovigni, F; Carossa, S

    2016-07-01

    During wound healing, biologically active molecules are released from platelets. The rationale of using platelet-rich plasma (PRP) relies on the concentration of bioactive molecules and subsequent delivery to healing sites. These bioactive molecules have been seldom simultaneously quantified within the same PRP preparation. In the present study, the flexible Bio-Plex system was employed to assess the concentration of a large range of cytokines, chemokines, and growth factors in 16 healthy volunteers so as to determine whether significant baseline differences may be found. Besides IL-1b, IL-1ra, IL-4, IL-6, IL-8, IL-12, IL-13, IL-17, INF-γ, TNF-α, MCP-1, MIP-1a, RANTES, bFGF, PDGF, and VEGF that were already quantified elsewhere, the authors reported also on the presence of IL-2, IL-5, IL-7, IL-9, IL-10, IL-15 G-CSF, GM-CSF, Eotaxin, CXCL10 chemokine (IP-10), and MIP 1b. Among the most interesting results, it is convenient to mention the high concentrations of the HIV-suppressive and inflammatory cytokine RANTES and a statistically significant difference between males and females in the content of PDGF-BB. These data are consistent with previous reports pointing out that gender, diet, and test system affect the results of platelet function in healthy subjects, but seem contradictory when compared to other quantification assays in serum and plasma. The inconsistencies affecting the experimental results found in literature, along with the variability found in the content of bioactive molecules, urge further research, hopefully in form of randomized controlled clinical trials, in order to find definitive evidence of the efficacy of PRP treatment in various pathologic and regenerative conditions. PMID:26950533

  11. 甲型H1N1流感患者血清KL-6、SP-D、TGF-β1和IL-8水平测定及分析

    Institute of Scientific and Technical Information of China (English)

    陈双峰; 陈海英; 张颖新; 李轲

    2010-01-01

    目的 观察甲型H1N1流感患者血清细胞因子Ⅱ型肺泡细胞表面抗原(KL-6)、肺表面活性蛋白D(SP-D)、转化生长因子-β1(TGF-β1)和IL-8水平变化及其临床价值. 方法采用ELISA法检测118例甲型H1N1流感患者(观察组)和40例健康查体者(对照组)血清KL-6、SP-D、TGF-β1和IL-8水平.结果 观察组血清KL-6、SP-D和IL-8水平显著高于对照组(尤以重症者为著),TGF-β1水平显著低于对照组,P分别<0.05、0.01. 结论 甲型H1N1流感患者血清KL-6、SP-D、TGF-β1和IL-8水平存在异常变化,检测 KL-6和SP-D水平对预测患者病情进展具有重要意义.

  12. Recombinant human growth-regulated oncogene-alpha induces T lymphocyte chemotaxis. A process regulated via IL-8 receptors by IFN-gamma, TNF-alpha, IL-4, IL-10, and IL-13

    DEFF Research Database (Denmark)

    Jinquan, T; Frydenberg, Jane; Mukaida, N;

    1995-01-01

    The human cytokine growth-regulated oncogene (GRO)-alpha is a small glycoprotein secreted by monocytes, endothelial cells, glycoprotein secreted by monocytes, endothelial cells, fibroblasts, synovial cells, and some tumor cells such as melanoma cells. It is structurally related to IL-8 and can...

  13. Enhanced IL-1β-induced IL-8 production in cystic fibrosis lung epithelial cells is dependent of both mitogen-activated protein kinases and NF-κB signaling

    International Nuclear Information System (INIS)

    Transcription nuclear factor-κB (NF-κB) is hyperactivated in cystic fibrosis (CF) lung epithelial cells, and participates in exaggerated IL-8 production in the CF lung. We recently found that rapid activation of NF-κB occurred in a CF lung epithelial IB3-1 cell line (CF cells) upon IL-1β stimulation, which was not observed in its CFTR-corrected lung epithelial S9 cell line (corrected cells). To test whether other signaling pathways such as that of mitogen-activated protein kinases (MAPKs) could be involved in IL-1β-induced IL-8 production of CF cells, we investigated ERK1/2, JNK, and p38MAP signaling compared to NF-κB. Within 30 min, exposure to IL-1β caused high activation of NF-κB, ERK1/2, p38MAP but not JNK in CF cells compared to corrected cells. Treatment of IL-1β-stimulated CF cells with a series of chemical inhibitors of NF-κB, ERK1/2, and p38MAP, when used separately, reduced slightly IL-8 production. However, when used together, these inhibitors caused a blockade in IL-1β-induced IL-8 production in CF cells. Understanding of the cross-talk between NF-κB and MAPKs signaling in CF lung epithelial cells may help in developing new therapeutics to reduce lung inflammation in patients with CF

  14. The Tumor-Promoting Flow of Cells Into, Within and Out of the Tumor Site: Regulation by the Inflammatory Axis of TNFα and Chemokines.

    Science.gov (United States)

    Ben-Baruch, Adit

    2012-08-01

    Tumors are dynamic organs, in which active processes of cell motility affect disease course by regulating the composition of cells at the tumor site. While sub-populations of tumor-promoting leukocytes are recruited inward and endothelial cell migration stands in the basis of vascular branching throughout the tumor, cancer cells make their way out of the primary site towards specific metastatic sites. This review describes the independent and cross-regulatory roles of inflammatory chemokines and of the inflammatory cytokine tumor necrosis factor α (TNFα) in determining cell motility processes that eventually have profound effects on tumor growth and metastasis. First, the effects of inflammatory chemokines such as CCL2 (MCP-1), CCL5 (RANTES) and CXCL8 (IL-8) are described, regulating the inward flow of leukocyte sub-populations with pro-tumoral activities, such as tumor-associated macrophages (TAM), myeloid-derived suppressor cells (MDSC), tumor-associated neutrophils (TAN), Th17 cells and Tregs. Then, the ability of inflammatory chemokines to induce endothelial cell migration, sprouting and tube formation is discussed, with its implications on tumor angiogenesis. This part is followed by an in depth description of the manners by which TNFα potentiates the above activities of the inflammatory chemokines, alongside with its ability to directly induce migratory processes in the tumor cells thus promoting metastasis. Note worthy is the ability of TNFα to induce in the tumor cells the important process of epithelial-to-mesenchymal transition (EMT). Emphasis is given to the ability of TNFα to establish an inflammatory network with the chemokines, and in parallel to form a cell re-modeling network together with transforming growth factor β (TGFβ). The review concludes by discussing the implications of such networks on disease course, and on the future design of therapeutic measures in cancer. PMID:22190050

  15. Chapter 8. Activation mechanisms of chemokine receptors

    DEFF Research Database (Denmark)

    Jensen, Pia C; Rosenkilde, Mette M

    2009-01-01

    Chemokine receptors belong to the large family of 7-transmembrane (7TM) G-protein-coupled receptors. These receptors are targeted and activated by a variety of different ligands, indicating that activation is a result of similar molecular mechanisms but not necessarily similar modes of ligand bin...

  16. 'Reverse gear' cellular movement mediated by chemokines.

    Science.gov (United States)

    Zlatopolskiy, A; Laurence, J

    2001-08-01

    We sought to model the mechanism by which leucocytes may be actively repulsed by a beta-chemokine signal. This model is used to interpret an apparent paradox in chemokine biology, whereby high levels of a T-cell chemoattractant, stromal cell derived factor-1 (SDF-1), are present in bone marrow and thymic tissues despite a paucity of mature T lymphocytes in these areas. We postulate the differential involvement in cell migration of the two binding sites on SDF-1 for its sole receptor, CXCR4, depending on whether high or low concentrations of SDF-1 are encountered by the cell. Site choice would be mediated by divergent affinities of the two binding interactions. We also propose differential signalling following SDF-1/CXCR4 interactions on the plasma membrane versus ligand/receptor complexes in endocytic vesicles. Preliminary data showing divergent susceptibility to kinase inhibitors depending on whether a cell is attracted to or repulsed by SDF-1, are consistent with this model. In terms of physical movement toward or away from a chemokine gradient, we compare the cycling of surface receptors during migration to the caterpillar drive of a tractor, which can change direction simply by altering the direction of rotation of its threads. Finally, the potential clinical implications of concentration-dependent, chemokine-based cell attraction and repulsion are discussed. PMID:11488980

  17. Cytokines and Chemokines in Irritant Contact Dermatitis

    OpenAIRE

    Haur Yueh Lee; Marco Stieger; Nikhil Yawalkar; Masato Kakeda

    2013-01-01

    Irritant contact dermatitis is a result of activated innate immune response to various external stimuli and consists of complex interplay which involves skin barrier disruption, cellular changes, and release of proinflammatory mediators. In this review, we will focus on key cytokines and chemokines involved in the pathogenesis of irritant contact dermatitis and also contrast the differences between allergic contact dermatitis and irritant contact dermatitis.

  18. Chemokine cooperativity is caused by competitive glycosaminoglycan binding

    NARCIS (Netherlands)

    Verkaar, F.; Offenbeek, J. van; Lee, M. van der; Lith, L.H. van; Watts, A.O.; Rops, A.L.; Aguilar, D.C.; Ziarek, J.J.; Vlag, J. van der; Handel, T.M.; Volkman, B.F.; Proudfoot, A.E.; Vischer, H.F.; Zaman, G.J.; Smit, M.J.

    2014-01-01

    Chemokines comprise a family of secreted proteins that activate G protein-coupled chemokine receptors and thereby control the migration of leukocytes during inflammation or immune surveillance. The positional information required for such migratory behavior is governed by the binding of chemokines t

  19. Chemokines and their receptors in central nervous system disease

    NARCIS (Netherlands)

    Biber, K; de Jong, EK; van Weering, HRJ; Boddeke, HWGM

    2006-01-01

    Almost a decade ago, it was discovered that the human deficiency virus (HIV) makes use of chemokine receptors to infect blood cells. This appreciation of the clinical relevance of specific chemokine receptors has initiated a considerable boost in the field of chemokine research. It is clear today th

  20. The role of CXC-chemokine receptor CXCR2 and suppressor of cytokine signaling-3 (SOCS-3) in renal cell carcinoma

    International Nuclear Information System (INIS)

    Chemokine receptor signaling pathways are implicated in the pathobiology of renal cell carcinoma (RCC). However, the clinical relevance of CXCR2 receptor, mediating the effects of all angiogenic chemokines, remains unclear. SOCS (suppressor of cytokine signaling)-3 is a negative regulator of cytokine-driven responses, contributing to interferon-α resistance commonly used to treat advanced RCC with limited information regarding its expression in RCC. In this study, CXCR2 and SOCS-3 were immunohistochemically investigated in 118 RCC cases in relation to interleukin (IL)-6 and (IL)-8, their downstream transducer phosphorylated (p-)STAT-3, and VEGF expression, being further correlated with microvascular characteristics, clinicopathological features and survival. In 30 cases relationships with hypoxia-inducible factors, i.e. HIF-1a, p53 and NF-κΒ (p65/RelA) were also examined. Validation of immunohistochemistry and further investigation of downstream transducers, p-JAK2 and p-c-Jun were evaluated by Western immunoblotting in 5 cases. Both CXCR2 and IL-8 were expressed by the neoplastic cells their levels being interrelated. CXCR2 strongly correlated with the levels of HIF-1a, p53 and p65/RelA in the neoplastic cells. Although SOCS-3 was simultaneously expressed with p-STAT-3, its levels tended to show an inverse relationship with p-JAK-2 and p-c-Jun in Western blots and were positively correlated with HIF-1a, p53 and p65/p65/RelA expression. Neither CXCR2 nor SOCS-3 correlated with the extent of microvascular network. IL-8 and CXCR2 expression was associated with high grade, advanced stage and the presence/number of metastases but only CXCR2 adversely affected survival in univariate analysis. Elevated SOCS-3 expression was associated with progression, the presence/number of metastasis and shortened survival in both univariate and multivariate analysis. Our findings implicate SOCS-3 overexpression in RCC metastasis and biologic aggressiveness advocating its

  1. Effects of urban air pollution on the inflammatory reaction: involvement of the chemokine pathways; Impact de la pollution atmospherique urbaine sur la reponse inflammatoire: implication des chimiokines

    Energy Technology Data Exchange (ETDEWEB)

    Fahy, O.

    2000-12-01

    Urban air pollution is both gaseous and particulate, and diesel exhausts are now the main source of particles. Diesel particles consist of a carbon core with multiple adsorbed organic compounds, among witch poly-aromatic hydrocarbons. These diesel particles and associated poly-aromatic hydrocarbons are likely to play a role in the recent increase in allergic diseases. In this study, we evaluated the effects of diesel organic extracts on the initiation and the orientation of the allergen-dependent inflammatory reaction by analyzing the dis-regulation of a family of mediators involved in cellular recruitment: the chemokines. We demonstrated that mononuclear cells and alveolar macrophages from normal subjects displayed a dis-regulation in pro-inflammatory chemokine expression and production (IL-8, MCP-1, RANTES) when exposed to diesel organic extracts. In addition we observed a synergy between the effects of diesel and allergen when cells from allergic patients were exposed to both simultaneously, leading to a strong over-production of chemokines, and to the increased capacity of recruiting effector cells such as neutrophils and eosinophils. The MAP kinase pathways seemed largely involved in the transduction of diesel and allergen stimulus, since a specific inhibition almost abolished the dis-regulation of chemokine production. Diesel and allergen also appeared to favour the establishment of a type 2 immune response (pro-allergenic), by preferentially recruiting Th2 lymphocytes via the dis-regulation of chemokine expression (MDC and IP-10). Finally, the humanized SCID mouse model grafted with autologous human skin allowed the in vivo evaluation of a local over-production of chemokine, by analyzing the cellular recruitment in the skin after intra-dermal injection of recombinant chemokines. This model appears useful for the study of the mechanisms of cellular recruitment by chemokines and the potential therapeutic approaches. In conclusion, our study underlines the

  2. Gene cloning and expression of Inertleukin-8(IL-8) from Orange-Spotted Grouper (Epinephelus coioides)%斜带石斑鱼白细胞介素8基因的克隆与表达分析

    Institute of Scientific and Technical Information of China (English)

    胡云凤; 孙军; 林小涛; 梁卉

    2010-01-01

    为了研究斜带石斑鱼(Epinephelus coioides)白细胞介素8(IL-8)的结构和功能,本实验对其基因序列进行了克隆和分析. 运用RACE-PCR方法,从斜带石斑鱼总RNA反转录cDNA库中获得了961 bp 长的cDNA全序列. 同时利用RT-PCR 技术,检测了微壁溶球菌诱导前后该基因在斜带石斑鱼体内不同组织之间的表达差异. 结果表明,斜带石斑鱼IL-8cDNA序列包含235 bp 的5′非编码区,438 bp的3′端非编码区和288 bp 的开放阅读框,编码95个氨基酸. 未诱导前,斜带石斑鱼IL-8基因主要在心、头肾、脾和肝脏中表达,在鳃和肠中量表达,在胃、肌和皮中几乎没有表达;诱导后,IL-8基因强烈表达于所有取样器官. 所获得的斜带石斑鱼IL-8基因是一种与炎症作用有关的CXC亚族趋化性因子.

  3. The effects of colloids or crystalloids on acute respiratory distress syndrome in swine (Sus scrofa models with severe sepsis: analysis on extravascular lung water, IL-8, and VCAM-1

    Directory of Open Access Journals (Sweden)

    Rismala Dewi

    2016-04-01

    Full Text Available Background: Acute respiratory distress syndrome (ARDS is a fatal complication of severe sepsis. Due to its higher molecular weight, the use of colloids in fluid resuscitation may be associated with fewer cases of ARDS compared to crystalloids. Extravascular lung water (EVLW elevation and levels of interleukin-8 (IL-8 and vascular cell adhesion molecule-1 (VCAM-1 have been studied as indicators playing a role in the pathogenesis of ARDS. The aim of the study was to determine the effects of colloid or crystalloid on the incidence of ARDS, elevation of EVLW, and levels of IL-8 and VCAM-1, in swine models with severe sepsis.Methods: This was a randomized trial conducted at the Laboratory of Experimental Surgery, School of Veterinary Medicine, IPB, using 22 healthy swine models with a body weight of 8 to 12 kg. Subjects were randomly allocated to receive either colloid or crystalloid fluid resuscitation. After administration of endotoxin, clinical signs of ARDS, EVLW, IL-8, and VCAM-1 were monitored during sepsis, severe sepsis, and one- and three hours after fluid resuscitation. Analysis of data using the Wilcoxon test , Kolmogorov-Smirnov test, Mann-Whitney test, unpaired t test.Results: Mild ARDS was more prevalent in the colloid group, while moderate ARDS was more frequent in the crystalloid group. EVLW elevation was lower in the colloid compared to the crystalloid group. There was no significant difference in IL-8 and VCAM-1 levels between the two groups.Conclusion: The use of colloids in fluid resuscitation does not decrease the probability of ARDS events compared to crystalloids. Compared to crystalloids, colloids are associated with a lower increase in EVLWI, but not with IL-8 or VCAM-1 levels.

  4. Anti-inflammatory activity of probiotic Bifidobacterium:Enhancement of IL-10 production in peripheral blood mononuclear cells from ulcerative colitis patients and inhibition of IL-8 secretion in HT-29 cells

    Institute of Scientific and Technical Information of China (English)

    Akemi Imaoka; Tatsuichiro Shima; Kimitoshi Kato; Shigeaki Mizuno; Toshiki Uehara; Satoshi Matsumoto; Hiromi Setoyama; Taeko Hara; Yoshinori Umesaki

    2008-01-01

    AIM: To determine the anti-inflammatory activity of probiotic Bifidobacteria in Bifidobacteria-fermented milk (BFM) which is effective against active ulcerative colitis (UC) and exacerbations of UC, and to explore the immunoregulatory mechanisms.METHODS: Peripheral blood mononuclear cells (PBMNC)from UC patients or HT-29 cells were co-cultured with heat-killed probiotic bacteria or culture supernatant of Bifidobacterium breve strain Yakult (BbrY) or Bifidobacterium bifidum strain Yakult (BbiY) to estimate the amount of IL-10 or IL-8 secreted.RESULTS: Both strains of probiotic Bifidobacteria contained in the BFM induced IL-10 production in PBMNC from UC patients, though BbrY was more effective than BbiY.Conditioned medium (CM) and DNA of both strains inhibited IL-8 secretion in HT-29 cells stimulated with TNF-α, whereas no such effect was observed with heatkilled bacteria.The inhibitory effect of CM derived from BbiY was greater than that of CM derived from BbrY.DNAs of the two strains had a comparable inhibitory activity against the secretion of IL-8.CM of BbiY induced a repression of IL-8 gene expression with a higher expression of IκB-ζ mRNA 4 h after culture of HT-29 cells compared to that in the absence of CM.CONCLUSION: Probiotic Bifidobacterium strains in BFM enhance IL-10 production in PBMNC and inhibit IL-8 secretion in intestinal epithelial cells, suggesting that BFM has anti-inflammatory effects against ulcerative colitis.

  5. Induction of IL-6 and inhibition of IL-8 secretion in the human airway cell line Calu-3 by urban particulate matter collected with a modified method of PM sampling

    International Nuclear Information System (INIS)

    Exposure to particulate matter (PM) induces inflammatory cytokines. In the present study, we evaluated the secretion of IL-6 and IL-8 by an airway cell line exposed to PM with a mean aerodynamic size equal to or less than 10 or 2.5 μm (PM10 and PM2.5, respectively) collected in Mexico City, using a modified high-volume sampling method avoiding the use of solvents or introducing membrane components into the samples. PM was collected on cellulose-nitrate (CN) membranes modified for collection on high-volume samplers. Composition of the particles was evaluated by particle-induced X-ray emission (PIXE) and scanning electron microscopy. The particles (10-160 μg/cm2) were tested on Calu-3 cells. Control cultures were exposed to LPS (10 ng/mL to 100 μg/mL) or silica (10-160 μg/cm2). IL-6 and IL-8 secretions were evaluated by ELISA. An average of 10 mg of PM was recovered form each cellulose-nitrate filter. No evidence of contamination from the filter was found. Cells exposed to PM10 presented an increase in the secretion of IL-6 (up to 400%), while IL-8 decreased (from 40% to levels below the detection limit). A similar but weaker effect was observed with PM2.5. In conclusion, our modified sampling method provides a large amount of urban PM free of membrane contamination. The urban particles induce a decrease in IL-8 secretion that contrasts with the LPS and silica effects. These results suggest that the regulation of IL-8 expression is different for urban particles (complex mixture containing combustion-related particles, soil and biologic components) than for biogenic compounds or pure mineral particles.

  6. Signal transducer and activator of transcription-3 licenses Toll-like receptor 4-dependent interleukin (IL)-6 and IL-8 production via IL-6 receptor-positive feedback in endometrial cells.

    Science.gov (United States)

    Cronin, J G; Kanamarlapudi, V; Thornton, C A; Sheldon, I M

    2016-09-01

    Interleukin 6 (IL-6), acting via the IL-6 receptor (IL6R) and signal transducer and activator of transcription-3 (STAT3), limits neutrophil recruitment once bacterial infections are resolved. Bovine endometritis is an exemplar mucosal disease, characterized by sustained neutrophil infiltration and elevated IL-6 and IL-8, a neutrophil chemoattractant, following postpartum Gram-negative bacterial infection. The present study examined the impact of the IL6R/STAT3 signaling pathway on IL-8 production by primary endometrial cells in response to short- or long-term exposure to lipopolysaccharide (LPS) from Gram-negative bacteria. Tyrosine phosphorylation of STAT3 is required for DNA binding and expression of specific targets genes. Immunoblotting indicated constitutive tyrosine phosphorylation of STAT3 in endometrial cells was impeded by acute exposure to LPS. After 24 h exposure to LPS, STAT3 returned to a tyrosine phosphorylated state, indicating cross-talk between the Toll-like receptor 4 (TLR4) and the IL6R/STAT3 signaling pathways. This was confirmed by short interfering RNA targeting the IL6R, which abrogated the accumulation of IL-6 and IL-8, induced by LPS. Furthermore, there was a differential endometrial cell response, as the accumulation of IL-6 and IL-8 was dependent on STAT3, suppressor of cytokine signaling 3, and Src kinase signaling in stromal cells, but not epithelial cells. In conclusion, positive feedback through the IL6R amplifies LPS-induced IL-6 and IL-8 production in the endometrium. These findings provide a mechanistic insight into how elevated IL-6 concentrations in the postpartum endometrium during bacterial infection leads to marked and sustained neutrophil infiltration. PMID:26813342

  7. The role of chemokines and chemokine receptors in eosinophil activation during inflammatory allergic reactions

    Directory of Open Access Journals (Sweden)

    Oliveira S.H.P.

    2003-01-01

    Full Text Available Chemokines are important chemotactic cytokines that play a fundamental role in the trafficking of leukocytes to sites of inflammation. They are also potent cell-activating factors, inducing cytokine and histamine release and free radical production, a fact that makes them particularly important in the pathogenesis of allergic inflammation. The action of chemokines is regulated at the level of agonist production and processing as well as at the level of receptor expression and coupling. Therefore, an analysis of the ligands must necessarily consider receptors. Eosinophils are target cells involved in the allergic inflammatory response since they are able to release a wide variety of mediators including CC and CXC chemokines and express their receptors. These mediators could damage the airway epithelial cells and might be important to stimulate other cells inducing an amplification of the allergic response. This review focuses on recently emerging data pertaining to the importance of chemokines and chemokine receptors in promoting eosinophil activation and migration during the allergic inflammatory process. The analysis of the function of eosinophils and their chemokine receptors during allergic inflammation might be a good approach to understanding the determinants of asthma severity and to developing novel therapies.

  8. 乳腺癌患者手术治疗前后血浆leptin和血清CA15-3、IL-8、hs-CRP检测的临床意义%Clinical Significance of Determination of Changes of Plasma Leptin and Serum CA15-3, IL-8,hs-CRP Levels Both Before and After Operation in Patients with Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    刘大林; 南云广; 刘敬西; 顾丹; 刘伟

    2012-01-01

    目的 探讨乳腺癌患者手术治疗前后血浆leptin和血清CA15-3、IL-8、hs-CRP水平的变化及临床意义.方法 应用放射免疫分析和免疫比浊法对31例乳腺癌患者进行了手术治疗前后血浆leptin和血清CA15-3、IL-8、hs-CRP检测,并与35名正常人作比较.结果 乳腺癌患者在手术治疗前血浆leptin和血清CA15-3、IL-8、hs-CRP水平非常显著地高于正常人组(P0.05).结论 血浆leptin和血清CA15-3、IL-8、hs-CRP水平的变化在乳腺癌的发生和发展中相互作用,观察其浓度的变化对探讨乳腺癌的发病机理、预防和治疗均有重要的临床价值.%Objective To study the clinical significance of changes of plasma leptin and serum CA15-3, IL-8, hs-CRP levels after operation in patients with breast cancer. Methods Plasma leptin and serum IL-8 ,CA15-3(with RIA) serum hs-CRP(with immu-noturbility method)levels were measured in 33 patients with breast cancer both before and after operation as well as in 35 normal con-trols. Results Before operation, plasma leptin and serum CA15-3,IL-8,hs-CRP levels were signifuMntiy higher than those in controls (P0.05). Conclusion These cytokines participated in the pathogenesis of breast cancer and monitoring the serum levels might be helpful to the prevention management of such malignancies.

  9. Epigallocatechin-3-gallate suppresses proinflammatory cytokines and chemokines induced by Toll-like receptor 9 agonists in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Mukherjee S

    2014-06-01

    Full Text Available Sushovita Mukherjee, Mohammad Adnan Siddiqui, Shubham Dayal, Yasmine Zakaria Ayoub, Krishnamurthy Malathi Department of Biological Sciences, University of Toledo, Toledo, OH, USA Abstract: Chronic inflammation of the prostate contributes to the increased risk of prostate cancer. Microbial pathogens in the prostate cause inflammation that leads to prostatitis and proliferative inflammatory atrophy frequently associated with the development of prostate cancer. Bacterial lipopolysaccharides and DNA mediate immune responses by engaging Toll-like receptor (TLR 4 and 9, respectively. Synthetic oligodeoxynucleotides containing CpG motifs (CpG-ODN mimic bacterial DNA and signal through TLR9 to initiate innate immune responses. Here, we show that stimulation of DU145, PC3, or LnCap prostate cancer cells by the TLR9 agonists, CpG-ODN, induces mRNA expression of IL-6, IL-8, CXCL1, IP-10, CCL5, and TGFβ. In addition, activity of matrix metalloproteinase (MMP-9 and -2 and cell migration increased on CpG-ODN treatment. Induction of cytokines and chemokines was mediated by NF-ΚB activation and translocation to the nucleus. Treatment with epigallocatechin-3-gallate (EGCG, the major constituent of green tea, prior to CpG-ODN stimulation, inhibits cytokine and chemokine gene induction, activity of MMP-9 and -2, and cell migration. EGCG treatment sequesters the p65 subunit of transcription factor NF-ΚB in the cytoplasm and inhibits transcriptional activity of the NF-ΚB-driven promoter in response to CpG-ODN. Our results suggest that the ability of the TLR9 agonists, CpG-ODN, to induce cytokines, chemokines, and MMP activity, as well as suppression by EGCG are independent of the androgen receptor and p53 status of the cells. EGCG may provide protective effects against inflammation in the prostate and benefit prostate cancer treatment. Keywords: CpG-ODN, EGCG, inflammation, NF-ΚB

  10. The CXC chemokine cCAF stimulates precocious deposition of ECM molecules by wound fibroblasts, accelerating development of granulation tissue

    Directory of Open Access Journals (Sweden)

    Li Qi-Jing

    2002-06-01

    Full Text Available Abstract Background During wound repair, fibroblasts orchestrate replacement of the provisional matrix formed during clotting with tenascin, cellular fibronectin and collagen III. These, in turn, are critical for migration of endothelial cells, keratinocytes and additional fibroblasts into the wound site. Fibroblasts are also important in the deposition of collagen I during scar formation. The CXC chemokine chicken Chemotactic and Angiogenic Factor (cCAF, is highly expressed by fibroblasts after wounding and during development of the granulation tissue, especially in areas where extracellular matrix (ECM is abundant. We hypothesized that cCAF stimulates fibroblasts to produce these matrix molecules. Results Here we show that this chemokine can stimulate precocious deposition of tenascin, fibronectin and collagen I, but not collagen III. Studies in culture and in vivo show that tenascin stimulation can also be achieved by the N-terminal 15 aas of the protein and occurs at the level of gene expression. In contrast, stimulation of fibronectin and collagen I both require the entire molecule and do not involve changes in gene expression. Fibronectin accumulation appears to be linked to tenascin production, and collagen I to decreased MMP-1 levels. In addition, cCAF is chemotactic for fibroblasts and accelerates their migration. Conclusions These previously unknown functions for chemokines suggest that cCAF, the chicken orthologue of human IL-8, enhances healing by rapidly chemoattracting fibroblasts into the wound site and stimulating them to produce ECM molecules, leading to precocious development of granulation tissue. This acceleration of the repair process may have important application to healing of impaired wounds.

  11. Chemokines CXCL10 and CCL2

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Sellebjerg, F; Jensen, C V;

    2001-01-01

    Studies of chemokines in cerebrospinal fluid (CSF) of patients with active multiple sclerosis (MS) have indicated that specific chemokines may have important roles in disease pathogenesis. We previously reported that CSF concentrations of CXCL10 (previously known as IP-10) were elevated in MS...... patients in relapse, whilst levels of CCL2 (MCP-1) were reduced. Here, we report a serial analysis of CSF CXCL10 and CCL2 concentrations in 22 patients with attacks of MS or acute optic neuritis (ON) treated with methylprednisolone, and 26 patients treated with placebo in two randomized controlled trials....... The levels of CXCL10 were higher in the patient group than in controls but two outliers in the control group also had high CSF concentrations of CXCL10. The CSF concentrations of CXCL10 did not change over time or after treatment. The CSF concentration of CXCL10 was positively correlated with the CSF...

  12. Effects of open lung concept on respiratory function and the levels of TNF-α、IL-8 after cardiopulmonary bypass%肺开放策略对体外循环后呼吸功能及TNF-α IL-8的影响

    Institute of Scientific and Technical Information of China (English)

    仲崇俊; 高增栋; 陆晨希; 薛群; 李峰; 姚小平; 刘麟

    2008-01-01

    目的 研究肺开放策略(OLC)对体外循环(CPB)手术后呼吸功能及肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)水平的影响.方法 选择24例心内直视手术患者,随机分成常规机械通气组(CMV)、早期肺开放组(EOL)、晚期肺开放组(LOL),EOL组在气管插管后实施肺开放策略,LOL组到达ICU后30 min实施肺开放策略:分别于术前、CPB后及到ICU后120、240及360 min记录各项呼吸指标:吸氧浓度、气道峰压、实际潮气量和呼气末气道正压(PEEP),计算动态肺顺应性.以酶联免疫吸附反应(ELISA)技术于术前、CPB后及到ICU后3、5、24和48 h测定TNF-α、IL-8水平.结果 CMV组及LOL组CPB后肺动态顺应性较术前明显下降(P<0.01);EOL组肺动态顺应性CPB后未见下降;LOL组经实施肺开放后肺动态顺应性逐渐上升,但在到ICU 120 min前肺动态顺应性仍低于EOL组(P<0.05);维持肺开放的最低PEEP LOL组高于EOL组(P<0.01).CPB后各组TNF-α水平均较术前显著升高(P<0.01),上升幅度EOL组低于LOL、CMV组,组间比较差异具有显著性(P<0.01);CPB后EOL组TNF-α水平逐渐下降,LOL、CMV组TNF-α水平进一步上升,在到达ICU后3 h达峰值.IL-8水平在两肺开放组呈显著下降趋势,EOL组在到ICU后24h恢复术前水平,LOL组在到ICU后48h后恢复术前水平,但CMV组各时点均显著高于术前(P<0.01).结论 OLC可减少CPB后炎性细胞因子的释放从而减轻CPB相关的肺损伤,早期实施OLC优于晚期实施OLC.

  13. 吸烟对COPD患者肺功能、IL-8及TNF-α的影响%The Effects of Smoking on Lung Function, Tumor Necrosis Factor-αand Interleukin-8 of Chronic Obstructive Pulmonary Disease

    Institute of Scientific and Technical Information of China (English)

    王立婧; 闫亮

    2014-01-01

    Obstructive To detect the lung function,the serum levels of TNF-α,IL-8 of chronic ob-structive pulmonary disease( COPD) patients with smoking and non-smoking. Methods Total of 50 cases of patients with COPD came to Tianjin baodi district people′s hospital During March to May 2012,and than di-vided into COPD smoking group and non-smoking group according to smoking, selected 26 healthy people who came to hospital as the control group. The serum levels of TNF-α,IL-8 were measured by enzyme linked immunosorbent assay ( ELISA) , at the same time test their lung function. Results The serum levels of TNF-α,IL-8 in COPD smoking group and non-smoking group were higher than that of healthy group, the TNF-α and IL-8 levels in smoking COPD group were significant higher than non-smoking COPD group( P<0. 05),and the level of FEV1% was significantly lower(P<0. 05). The levels of TNF-αand IL-8 in smok-ing COPD group were positively correlated with smoking index,and the level of FEV1% was significant nega-tively correlated with smoking index(r= -0. 516,P<0. 001)Conclusion The levels of TNF-a and IL-8 are raised by COPD and smoking, giving up smoking is the important measure for preventing and reducing the incidence of COPD. Reducing the level of inflammation factors is a new strategy to improve the level of COPD airway inflammation of the progress.%目的:通过测定慢性阻塞性肺疾病( COPD)吸烟与非吸烟患者及健康人群的肺功能以及TNF-α、IL-8水平,探讨吸烟对COPD患者肺功能、TNF-α、IL-8水平的影响。方法选择2012年3~5月来天津市宝坻区人民医院呼吸科门诊就诊的50例处于稳定期的COPD患者作为研究对象,根据是否吸烟分为COPD吸烟组和COPD非吸烟组,选取同期来医院进行健康体检的26健康人作为健康对照组。采用酶联免疫吸附法测定所有受试者血清TNF-α、IL-8的水平,同时检测受试者的肺功能。结果 COPD吸烟组及COPD非吸烟组中受试者IL-8

  14. Chemokines and Chemokine Receptors as Novel Therapeutic Targets in Rheumatoid Arthritis (RA): Inhibitory Effects of Traditional Chinese Medicinal Components

    Institute of Scientific and Technical Information of China (English)

    Xin Chen; Joost J. Oppenheim; O.M.Zack Howard

    2004-01-01

    Chemokines belong to a large family of inflammatory cytokines responsible for migration and accumulation of leukocytes at inflammatory sites. Over the past decade, accumulating evidence indicated a crucial role for chemokines and chemokine receptors in the pathophysiology of rheumatoid arthritis (RA). RA is a chronic autoimmune disease in which the synovial tissue is heavily infiltrated by leukocytes. Chemokines play an important role in the infiltration, localization, retention of infiltrating leukocytes and generation of ectopic germinal centers in the inflamed synovium. Recent evidence also suggests that identification of inhibitors directly targeting chemokines or their receptors may provide a novel therapeutic strategy in RA. Traditional Chinese medicinals (TCMs) have a long history in the treatment of inflammatory joint disease. The basis for the clinical benefits of TCM remains largely unclear. Our studies have led to the identification of numerous novel chemokine/chemokine receptor inhibitors present in anti-inflammatory TCMs. All of these inhibitors were previously reported by other researchers to have anti-arthritic effect, which may be attributable, at least in part, to their inhibitory effect on chemokine and/or chemokine receptor. Therefore, identification of agents capable of targeting chemokine/chemokine receptor interactions has suggested a mechanism of action for several TCM components and provided a means of identifying additional anti-RA TCM. Thus, this approach may lead to the discovery of new inhibitors of chemokines or chemokine receptors that can be used to treat diseases associated with inappropriately overactive chemokine mediated inflammatory reactions. Cellular & Molecular Immunology. 2004;1(5):336-342.

  15. Comparisons of IL-8, ROS and p53 responses in human lung epithelial cells exposed to two extracts of PM2.5 collected from an e-waste recycling area, China

    Science.gov (United States)

    Yang, Fangxing; Jin, Shiwei; Xu, Ying; Lu, Yuanan

    2011-04-01

    To identify the different effects of organic-soluble and water-soluble pollutants adsorbed on PM2.5 (PM: particulate matter) released from e-waste (electrical/electronic waste) on inflammatory response, oxidative stress and DNA damage, interleukin-8 (IL-8), reactive oxygen species (ROS) and p53 protein levels were determined and compared in human lung epithelial A549 cells exposed to extracts of PM2.5 collected from two sampling sites in an e-waste recycling area in China. It is found that both extracts induced increases of IL-8 release, ROS production and p53 protein expression. The differences between the organic-soluble and water-soluble extracts were determined as of significance for ROS production (p waste recycling areas could lead to inflammatory response, oxidative stress and DNA damage, and the organic-soluble extracts had higher potential to induce such adverse effects on human health.

  16. 鞣花酸对前列腺癌细胞PC3增殖迁移趋化及IL-8信号通路抑制作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    李文仿; 欧琴; 赵宗彬; 王耕

    2014-01-01

    Objective To investigate the mechanism of ellagic acid on PC3 prostate cancer cells proliferation inhibition and Il-8 signal pathway inhibition effect.Methods Ellagic acid with 6μg/ml,12μg/ml different concentrations to treat prostate cancer cell PC3,ellagic acid on prostate cancer cells PC3 cell proliferation,cell movement,cell chemotaxis,and ellagic acid in prostate cancer cell PC3 IL - 8 signal activation were investigated,with the target to explore the ellagic acid inhibition mechanism of PC3 prostate cancer cells.Results Ellagic acid not only inhibits prostate cancer cell proliferation,its migrationand chemotactic movement,but also significantly inhibits IL - 8’s activation of prostate cancer cells,which indicates the ellagic acid as as inhibitor of prostate cancer with its important role inprevention of its recurrence and metastasis.Conclusion Ellagic acid can inhibit PC3 prostate cancer cell proliferation,migration and chemotactic movement,ellagic acid can inhibit IL - 8 signal activation of prostate cancer cells,indicates the importance of ellagic acid inhibitor,prostate cancerin the prevention of prostate cancer recurrence and metastasis may have important role.%目的:探讨鞣花酸对前列腺癌细胞PC3的增殖、迁移、趋化作用,以及对前列腺癌细胞PC3中IL-8信号通路的抑制作用。方法采用6μg/ml、12μg/ml浓度的鞣花酸分别处理前列腺癌细胞PC3,通过细胞计数实验观察PC3的细胞增殖、通过细胞划痕实验观察癌细胞的运动、通过Transwell趋化小室实验观察细胞趋化作用,同时观察6μg/ml、12μg/ml浓度的鞣花酸对前列腺癌细胞PC3中IL-8信号激活的抑制作用,探讨鞣花酸对前列腺癌细胞PC3的抑制作用机制。结果与对照组比较,经6μg/ml、12μg/ml浓度的鞣花酸对前列腺癌细胞PC3处理24h、48h、72h时,对抑制细胞增殖、迁移及趋化运动均有明显作用(P<0.05);6μg/ml、12μg/ml浓度的鞣花酸能明显抑制IL

  17. DA-9601, a standardized extract of Artemisia asiatica, blocks TNF-α-induced IL-8 and CCL20 production by inhibiting p38 kinase and NF-κB pathways in human gastric epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Suck-Chei Choi; Kang-Min Lee; Won-Jung Lee; Jae-Sik Park; Chang-Yell Shin; Tae-Young Oh; Chang-Duk Jun; Eun-Ju Choi; Hyun-Mee Oh; SungGa Lee; Jeong-Kun Lee; Meung-Su Lee; Yong-Il Shin; Suck-Jun Choi; Jeong-Ryong Chae

    2006-01-01

    AIM: To investigate whether, or how, DA-9601, which is a new gastroprotective agent, inhibits TNF-α-induced inflammatory signals in gastric epithelial AGS cells. METHODS: Cell viability was determined by MTT assay. IL-8 and CCL20 promoter activities were determined by a luciferease reporter gene assay. NF-κB-dependent transcriptional activity was determined by I-κBα degradation, NF-κB p65 nuclear translocation and a luciferase activity assay. IL-8 and CCL20 gene expression and protein secretion were determined by RT-PCR and an enzymelinked immunosorbent assay (ELISA). Total and phosphorylated forms of mitogen-activated protein kinases (MAPKs) were determined by Western blot. RESULTS: Treatment of AGS cells with DA-9601 reduced TNF-α-induced IL-8 and CCL20 promoter activities, as well as their gene expression and protein release. TNF-α also induced NF-κB-dependent transcriptional activity in AGS cells. In contrast, in cells treated with DA-9601, TNF-α-induced NF-κB activity was significantly blocked. Although all three MAP kinase family members were phosphorylated in response to TNF-α, a selective inhibitor of p38 kinase SB203580 only could inhibit both NF κB-dependent transcriptional activity and IL-8 and CCL20 production, suggesting a potential link between p38 kinase and NF-κB-dependent pathways in AGS cells. Interestingly, DA-9601 also selectively inhibited p38 kinase phosphorylation induced by TNF-α.CONCLUSION: DA-9601 blocked TNF-α-mediated inflammatory signals by potentially modulating the p38 kinase pathway and/or a signal leading to NF-κB dependent pathways in gastric epithelial cells.

  18. TNF-alpha and IL-8: serum levels and gene polymorphisms (-308G>A and -251A>T) are associated with classical biomarkers and medical history in children with sickle cell anemia.

    Science.gov (United States)

    Cajado, C; Cerqueira, B A V; Couto, F D; Moura-Neto, J P; Vilas-Boas, W; Dorea, M J; Lyra, I M; Barbosa, C G; Reis, M G; Goncalves, M S

    2011-11-01

    Sickle cell anemia (SCA) is a disorder characterized by a heterogeneous clinical outcome. In the present study, we investigated the associations between Tumor Necrosis Factor-alpha (TNF-alpha) -308G>A and Interleukin 8 (IL-8) -251A>T gene polymorphisms, medical history and classical biomarkers in children with steady-state SCA. In total, 210 SCA patients aged 2-21 years and 200 healthy controls were studied. Gene polymorphisms, betaS-globin haplotypes and a 3.7-kb deletion in alpha2-thalassemia (α2-thal3.7 kb) were investigated by PCR/RFLP analysis, and cytokine levels were determined by ELISA. Splenomegaly (p=.032) was more prevalent among children younger than 5 years of age. The A allele of the TNF-alpha -308G>A gene polymorphism and the presence of α2-thal3.7 kb were associated with an increase risk of splenic sequestration events (p=.001; p=.046), while the T allele of the IL-8 -251A>T gene polymorphism was considered to be a protective factor for splenomegaly events (p=.032). Moreover, the A allele of the TNF-alpha -308G>A gene polymorphism was associated with high TNF-alpha levels (p=.021), and the hemoglobin F and hemoglobin S haplotypes were correlated with serum levels of IL-8. The logistic regression analysis showed significant effects of the TNF-alpha and IL-8 gene polymorphisms, beta(S)-globin gene haplotypes and α2-thal3.7 kb on the occurrence of splenic sequestration events. Our study emphasizes that the identification of new genetic and immunological biomarkers and their associations with classical markers is an important strategy to elucidate the underlying causes of different SCA phenotypes and their effects on patient outcome. PMID:21802960

  19. Sour cherry seed kernel extract increases heme oxygenase-1 expression and decreases representation of CD3+ TNF-α+ and CD3+IL-8+ subpopulations in peripheral blood leukocyte cultures from type 2 diabetes patients.

    Science.gov (United States)

    Mahmoud, Fadia F; Al-Awadhi, Rana; Haines, David D; Dashti, Ali; Dashti, Hussain; Al-Ozairi, Ebaa; Bak, Istvan; Tosaki, Arpad

    2013-05-01

    The present study evaluates a hypothesis that sour cherry (Prunus cerasus) seed extracts (SCE) modulate CD3+ T lymphocyte activity in ways predictive of potential for uses of SCE in management of inflammatory diseases. Peripheral blood mononuclear cells (PBMC) from 12 type 2 diabetes (T2DM) patients and eight healthy control subjects were cultured 24 h with 100 ng/ml lipopolysaccharide (LPS) to increase inflammatory signaling and co-incubated with 0.5-100 µg/ml SCE. Cultures were evaluated by two-color flow cytometry for percent representation of CD3+ IL8+ and CD3+TNF-α cells which express interleukin-8 (IL-8), and tumor necrosis factor-α, (TNF-α+) respectively, and by enzyme-linked immunoassay for lymphocyte-associated heme oxygenase-1 (HO-1, known to be induced by SCE). SCE dosage ranges of 0.5-100 µg/ml in cell cultures significantly suppressed LPS-increased CD3+TNF-α+ and CD3+IL8+ representation from all participants (p < 0.05), with greater pharmacological effect noted in suppression of CD3+TNF-α+ noted in cells from T2DM patients versus healthy control subjects. These effects correlated with increased HO-1 expression in SCE-treated PBMC from all subjects (p < 0.05). Since TNF-α and IL-8 are diagnostic/prognostic biomarkers for many inflammatory syndromes, the capacity of SCE to down-regulate representation of cells that express them suggests potential for therapeutic use of SCE in T2DM and other diseases. PMID:22848037

  20. Dysfunctional Activation of Neurotensin/IL-8 Pathway in Hepatocellular Carcinoma Is Associated with Increased Inflammatory Response in Microenvironment, More Epithelial Mesenchymal Transition in Cancer and Worse Prognosis in Patients

    OpenAIRE

    Yu, Jinpu; Ren, Xiubao; Chen, Yongzi; Liu, Pengpeng; Wei, Xiyin; Li, Hui; Ying, GuoGuang; Chen, Kexin; WINKLER, HANS; Hao, Xishan

    2013-01-01

    Aim To investigate the role of neurotensin (NTS) in hepatocellular carcinoma (HCC) sub- grouping and the clinical and pathological significance of activation of NTS/IL-8 pathway in HCC. Methods The genome-wide gene expression profiling were conducted in 10 pairs of cancer tissues and corresponding normal adjacent tissues samples using Affymetrix GeneChip® Human Genome U133 Plus 2.0 microarray to screen differentially expressing genes and enrich dysfunctional activated pathways among different...

  1. Cascade quantum teleportation

    Institute of Scientific and Technical Information of China (English)

    ZHOU Nan-run; GONG Li-hua; LIU Ye

    2006-01-01

    In this letter a cascade quantum teleportation scheme is proposed. The proposed scheme needs less local quantum operations than those of quantum multi-teleportation. A quantum teleportation scheme based on entanglement swapping is presented and compared with the cascade quantum teleportation scheme. Those two schemes can effectively teleport quantum information and extend the distance of quantum communication.

  2. Influence of acute psychosocial stress on IL-8 and IL-18 in peripheral blood of patients with psoriasis vulgaris%急性社会心理应激对寻常型银屑病患者外周血IL-8和IL-18的影响

    Institute of Scientific and Technical Information of China (English)

    严月华; 宋韬; 翟晓翔; 吴剑波; 盛晚香; 缪泽群

    2010-01-01

    目的:评价急性社会心理应激对寻常型银屑病患者外周血单核细胞分泌细胞因子的影响.方法:在社会应激测试(TSST)前10 min和测试后1、10、20、60 min采集患者和健康对照者外周血,分离培养外周血单核细胞,用双抗体夹心ELISA 法检测培养上清液中IL-8和IL-18的含量.结果:TSST测试后20 min外周血单核细胞培养上清液中IL-18的含量升高(P<0.05).结论:急性社会心理应激可引起寻常型银屑病患者外周血单核细胞分泌IL-18的增加,这可能是社会心理应激使银屑病发生和加重的部分中介机制.

  3. Immunohistochemical Analysis of IL-6, IL-8/CXCR2 Axis,  Tyrp-STAT-3, and SOCS-3 in Lymph Nodes from Patients with Chronic Lymphocytic Leukemia: Correlation between Microvascular Characteristics and Prognostic Significance

    Directory of Open Access Journals (Sweden)

    Georgia Levidou

    2014-01-01

    Full Text Available A number of studies have looked into the pathophysiological role of angiogenesis in CLL, but the results have often been inconsistent. We aimed to gain direct insight into the angiogenic process in lymph nodes involved by CLL, focusing on proangiogenic cytokines and microvessel morphometry. The tissue levels of VEGF, Th-2 cytokines IL-6 and IL-8, IL-8 receptor CXCR2, and tyrosine p-STAT-3/SOCS-3 axis modulating cytokine expression were evaluated immunohistochemically in 62 CLL/SLL cases. Microvascular characteristics were evaluated by image analysis. Results were analyzed with regard to clinicopathological characteristics. Proliferation centers (PCs were less well vascularised compared to non-PC areas. IL-8 and CXCR2 expression was distinctly uncommon as opposed to IL-6, VEGF and SOCS-3, which were detected in the vast majority of cases. The latter two molecule expressions were more pronounced in the PCs in ∼40% of the cases. p-STAT-3 immunoreactivity was recorded in 66.67% of the cases with a predilection for PCs. Microvessel morphometry was unrelated to proangiogenic cytokines, p-STAT-3, SOCS-3, or survival. Microvascular caliber and VEGF expression were higher in Binet stage A, whereasIL-6 expression was higher in stage C. VEGF and p-STAT-3 exerted a favorable effect on progression, which remained significant in multivariate analysis, thereby constituting potential outcome predictors in CLL patients.

  4. Biased and g protein-independent signaling of chemokine receptors

    DEFF Research Database (Denmark)

    Steen, Anne; Larsen, Olav; Thiele, Stefanie;

    2014-01-01

    not be absolute, i.e., full versus no activation. Here we discuss biased signaling in the chemokine system, including the structural basis for biased signaling in chemokine receptors, as well as in class A 7TM receptors in general. This includes overall helical movements and the contributions of micro......-switches based on recently published 7TM crystals and molecular dynamics studies. All three forms of biased signaling are abundant in the chemokine system. This challenges our understanding of "classic" redundancy inevitably ascribed to this system, where multiple chemokines bind to the same receptor and where...... a single chemokine may bind to several receptors - in both cases with the same functional outcome. The ubiquitous biased signaling confers a hitherto unknown specificity to the chemokine system with a complex interaction pattern that is better described as promiscuous with context-defined roles...

  5. Lipopolysaccharide-Induced Profiles of Cytokine, Chemokine, and Growth Factors Produced by Human Decidual Cells Are Altered by Lactobacillus rhamnosus GR-1 Supernatant.

    Science.gov (United States)

    Li, Wei; Yang, Siwen; Kim, Sung O; Reid, Gregor; Challis, John R G; Bocking, Alan D

    2014-01-15

    The aim of this study was to assess the effects of bacterial lipopolysaccharide (LPS) and Lactobacillus rhamnosus GR-1 supernatant (GR-1SN) on secretion profiles of cytokines, chemokines, and growth factors from primary cultures of human decidual cells. Lipopolysaccharide significantly increased the output of proinflammatory cytokines (interleukin [IL]-1B, IL-2, IL-6, IL-12p70, IL-15, IL-17A, interferon gamma [IFN-γ], and tumor necrosis factor [TNF]); anti-inflammatory cytokines (IL-1RN, IL-4, IL-9, and IL-10); chemokines (IL-8, eotaxin, IFN-inducible protein 10 [IP-10], monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein-1α [MIP-1α], macrophage inflammatory protein-1β [MIP-1β], and regulated on activation normal T cell expressed and secreted [RANTES]); and growth factors (granulocyte colony-stimulating factor [CSF] 3, CSF-2, and vascular endothelial growth factor A [VEGFA]). Lactobacillus rhamnosus GR-1SN alone significantly increased CSF-3, MIP-1α MIP-1β, and RANTES but decreased IL-15 and IP-10 output. The GR-1SN also significantly or partially reduced LPS-induced proinflammatory cytokines TNF, IFN-γ, IL-1β, IL-2 IL-6, IL-12p70, IL-15, IL-17, and IP-10; partially reduced LPS-induced anti-inflammatory cytokines IL-1RN, IL-4 and IL-10, and LPS-induced VEGFA output but did not affect CSF-3, MIP-1α, MIP-1β, MCP-1, IL-8, and IL-9. Our results demonstrate that GR-1SN attenuates the inflammatory responses to LPS by human decidual cells, suggesting its potential role in ameliorating intrauterine infection. PMID:24429676

  6. CXC and CC Chemokines as Angiogenic Modulators in Nonhaematological Tumors

    Science.gov (United States)

    Bracarda, Sergio; Nabissi, Massimo; Massari, Francesco; Bria, Emilio; Tortora, Giampaolo; Santoni, Giorgio; Cascinu, Stefano

    2014-01-01

    Chemokines are a superfamily of structurally homologous heparin-binding proteins that includes potent inducers and inhibitors of angiogenesis. The imbalance between angiogenic and angiostatic chemokine activities can lead to abnormalities, such as chronic inflammation, dysplastic transformation, and even tumor development and spreading. In this review, we summarize the current literature regarding the role of chemokines as modulators of tumor angiogenesis and their potential role as therapeutic targets in patients with nonhaematological tumors. PMID:24971349

  7. CXC and CC Chemokines as Angiogenic Modulators in Nonhaematological Tumors

    Directory of Open Access Journals (Sweden)

    Matteo Santoni

    2014-01-01

    Full Text Available Chemokines are a superfamily of structurally homologous heparin-binding proteins that includes potent inducers and inhibitors of angiogenesis. The imbalance between angiogenic and angiostatic chemokine activities can lead to abnormalities, such as chronic inflammation, dysplastic transformation, and even tumor development and spreading. In this review, we summarize the current literature regarding the role of chemokines as modulators of tumor angiogenesis and their potential role as therapeutic targets in patients with nonhaematological tumors.

  8. 急性心肌梗死后急性期室壁瘤形成患者血浆BNP、cTnI、CK MB、IL 8的变化研究

    Institute of Scientific and Technical Information of China (English)

    刘铁楠; 吴春涛; 于海燕; 李素新; 周云慧; 白华; 张蕴丽; 王立霞; 吴曼

    2015-01-01

    目的:观察急性心肌梗死(AMI)后急性期室壁瘤(AVA)形成患者血浆脑钠素(BNP)、心肌肌钙蛋白 I(cTnI)、肌酸激酶同工酶(CK MB)、白细胞介素8(IL 8)的变化,并探讨其心功能之间关系。方法选择急性前壁心肌梗死患者48例作为研究对象,根据是否形成急性室壁瘤分为 AVA组(21例)及非 AVA组(27例),均于 AMI发作6h、12h、18h、1 d、2 d、3 d测定血浆BNP、cTnI、CK MB、IL 8水平,探讨其水平变化,并分析其与AVA之间相关关系。结果 AVA组6h、12h、18h、1 d、2 d、3 d BNP水平均显著高于非 AVA组(P<0.05);AVA组梗死后12h、1 d、2 d cTnI水平均高于非AVA组(P<0.05);AVA组梗死发生后12h、1 d、2 d、3 d CK MB水平高于非 AVA组(P<0.05);AVA组梗死发生后12h、18h、2 d、3 d IL 8水平均显著高于非 AVA组(P<0.05);血浆BNP、cTnI、CK MB、IL 8水平与急性期室壁瘤形成具有明显正相关关系(r值分别为0.527、0.512、0.615、0.498,P<0.05)。结论急性心肌梗死后急性期室壁瘤形成患者血浆BNP、cTnI、CKMB、IL 8水平变化具有一定特点,且与心功能具有重要关联。

  9. Pouncing on the chemokine receptor Chimera.

    Science.gov (United States)

    Mascolini, M

    1997-08-01

    Scientists are seeking to unravel the mystery of chemokine receptors in an attempt to develop treatments for HIV infection; however, receptor experts are realizing that the picture is more complicated than they first imagined. Scientists want to know, among other things, what parts of each coreceptor are essential for viral fusion with target cells, what makes macrophage-tropic viruses switch their preference to T-lymphocytes, why HIV goes after chemokine receptors in the first place, and how fusion and entry occur. Other issues discussed include whether blocking coreceptors for HIV will actually curb this disease, virus turnover in monkey studies showing that SIV may go through the cycle as many as 100 times per day, and studies showing that the first days of infection may predict the course of disease. Final comments concern the use of ritonavir plus indinavir in treatment combinations for children with HIV and the latest progress toward vaccine development. Understanding these and other puzzles might help scientists to develop drugs to block receptors active in HIV infection and perhaps curb HIV. More than 14 biotechnology and pharmaceutical firms are working to design coreceptor blockers, despite the opinions of several leading researchers that the drugs are not terribly promising. Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Disease (NIAID), notes that a famous attempt to block HIV's primary receptor failed, and David Ho, the man who demonstrated why CD4 would not work as therapy, is similarly cautious. According to Ho, drug makers will have no trouble developing compounds that keep HIV off chemokine receptors, such as CCR5 or CXCR4, but whether those compounds will slow disease progression is another question. PMID:11364629

  10. Genomic organization, annotation, and ligand-receptor inferences of chicken chemokines and chemokine receptor genes based on comparative genomics

    Directory of Open Access Journals (Sweden)

    Sze Sing-Hoi

    2005-03-01

    Full Text Available Abstract Background Chemokines and their receptors play important roles in host defense, organogenesis, hematopoiesis, and neuronal communication. Forty-two chemokines and 19 cognate receptors have been found in the human genome. Prior to this report, only 11 chicken chemokines and 7 receptors had been reported. The objectives of this study were to systematically identify chicken chemokines and their cognate receptor genes in the chicken genome and to annotate these genes and ligand-receptor binding by a comparative genomics approach. Results Twenty-three chemokine and 14 chemokine receptor genes were identified in the chicken genome. All of the chicken chemokines contained a conserved CC, CXC, CX3C, or XC motif, whereas all the chemokine receptors had seven conserved transmembrane helices, four extracellular domains with a conserved cysteine, and a conserved DRYLAIV sequence in the second intracellular domain. The number of coding exons in these genes and the syntenies are highly conserved between human, mouse, and chicken although the amino acid sequence homologies are generally low between mammalian and chicken chemokines. Chicken genes were named with the systematic nomenclature used in humans and mice based on phylogeny, synteny, and sequence homology. Conclusion The independent nomenclature of chicken chemokines and chemokine receptors suggests that the chicken may have ligand-receptor pairings similar to mammals. All identified chicken chemokines and their cognate receptors were identified in the chicken genome except CCR9, whose ligand was not identified in this study. The organization of these genes suggests that there were a substantial number of these genes present before divergence between aves and mammals and more gene duplications of CC, CXC, CCR, and CXCR subfamilies in mammals than in aves after the divergence.

  11. Cascade Lake: A Novel

    OpenAIRE

    Pack, Camille Marian

    2009-01-01

    Twenty-two-year-old Macy Oman narrates the book in retrospect from Cascade, Oregon, where she is visiting her mother. Macy's father moved with her to Portland shortly after the accidental death of her brother, Nick, seven years before the narration begins. Macy's mother stayed behind in Cascade. Thematically the work centers on the emotional repercussions of these losses. Macy's, and her older lover Jason's, involvement with Nick's death is unknown to everyone. Her guilt and her mother's perc...

  12. Distinct chemokine receptor and cytokine expression profile in secondary progressive MS

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Sellebjerg, F

    2001-01-01

    Chemokines, small chemotactic cytokines, have been implicated in active relapsing-remitting MS (RRMS). However, the role of chemokines and chemokine receptors has not been specifically studied in secondary progressive MS (SPMS)....

  13. Neonatal chemokine levels and risk of autism spectrum disorders

    DEFF Research Database (Denmark)

    Abdallah, Morsi; Larsen, Nanna; Grove, Jakob;

    2013-01-01

    A potential role of chemokines in the pathophysiology of Autism Spectrum Disorders (ASDs) has been previously suggested. In a recent study we examined levels of three inflammatory chemokines (MCP-1, MIP-1a and RANTES) in samples of amniotic fluid of children diagnosed later in life with ASD...

  14. Chemokine receptor CCR5 in interferon-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Kristiansen, T B; Wittenhagen, P;

    2007-01-01

    To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta).......To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta)....

  15. Chemokine-Derived Peptides: Novel Antimicrobial and Antineoplasic Agents

    Science.gov (United States)

    Valdivia-Silva, Julio; Medina-Tamayo, Jaciel; Garcia-Zepeda, Eduardo A.

    2015-01-01

    Chemokines are a burgeoning family of chemotactic cytokines displaying a broad array of functions such as regulation of homeostatic leukocyte traffic and development, as well as activating the innate immune system. Their role in controlling early and late inflammatory stages is now well recognized. An improper balance either in chemokine synthesis or chemokine receptor expression contributes to various pathological disorders making chemokines and their receptors a useful therapeutic target. Research in this area is progressing rapidly, and development of novel agents based on chemokine/chemokine receptors antagonist functions are emerging as attractive alternative drugs. Some of these novel agents include generation of chemokine-derived peptides (CDP) with potential agonist and antagonist effects on inflammation, cancer and against bacterial infections. CDP have been generated mainly from N- and C-terminus chemokine sequences with subsequent modifications such as truncations or elongations. In this review, we present a glimpse of the different pharmacological actions reported for CDP and our current understanding regarding the potential use of CDP alone or as part of the novel therapies proposed in the treatment of microbial infections and cancer. PMID:26062132

  16. Neuronal chemokines : Versatile messengers in central nervous system cell interaction

    NARCIS (Netherlands)

    de Haas, A. H.; van Weering, H. R. J.; de Jong, E. K.; Boddeke, H. W. G. M.; Biber, K. P. H.

    2007-01-01

    Whereas chemokines are well known for their ability to induce cell migration, only recently it became evident that chemokines also control a variety of other cell functions and are versatile messengers in the interaction between a diversity of cell types. In the central nervous system (CNS), chemoki

  17. Chemokine-Derived Peptides: Novel Antimicrobial and Antineoplasic Agents

    Directory of Open Access Journals (Sweden)

    Julio Valdivia-Silva

    2015-06-01

    Full Text Available Chemokines are a burgeoning family of chemotactic cytokines displaying a broad array of functions such as regulation of homeostatic leukocyte traffic and development, as well as activating the innate immune system. Their role in controlling early and late inflammatory stages is now well recognized. An improper balance either in chemokine synthesis or chemokine receptor expression contributes to various pathological disorders making chemokines and their receptors a useful therapeutic target. Research in this area is progressing rapidly, and development of novel agents based on chemokine/ chemokine receptors antagonist functions are emerging as attractive alternative drugs. Some of these novel agents include generation of chemokine-derived peptides (CDP with potential agonist and antagonist effects on inflammation, cancer and against bacterial infections. CDP have been generated mainly from N- and C-terminus chemokine sequences with subsequent modifications such as truncations or elongations. In this review, we present a glimpse of the different pharmacological actions reported for CDP and our current understanding regarding the potential use of CDP alone or as part of the novel therapies proposed in the treatment of microbial infections and cancer.

  18. The atypical chemokine receptor D6 contributes to the development of experimental colitis1

    OpenAIRE

    Bordon, Yvonne; Hansell, Chris A H; Sester, David P; Clarke, Mairi; Mowat, Allan McI; Nibbs, Robert J B

    2009-01-01

    Pro-inflammatory CC chemokines control leukocyte recruitment and function during inflammation by engaging chemokine receptors expressed on circulating leukocytes. The D6 chemokine receptor can bind several of these chemokines but appears unable to couple to signal transduction pathways or direct cell migration. Instead, D6 has been proposed to act as a chemokine scavenger, removing pro-inflammatory chemokines to dampen leukocyte responses. In this report, we have examined the role of D6 in th...

  19. Production of Recombinant Chemokines and Validation of Refolding.

    Science.gov (United States)

    Veldkamp, Christopher T; Koplinski, Chad A; Jensen, Davin R; Peterson, Francis C; Smits, Kaitlin M; Smith, Brittney L; Johnson, Scott K; Lettieri, Christina; Buchholz, Wallace G; Solheim, Joyce C; Volkman, Brian F

    2016-01-01

    The diverse roles of chemokines in normal immune function and many human diseases have motivated numerous investigations into the structure and function of this family of proteins. Recombinant chemokines are often used to study how chemokines coordinate the trafficking of immune cells in various biological contexts. A reliable source of biologically active protein is vital for any in vitro or in vivo functional analysis. In this chapter, we describe a general method for the production of recombinant chemokines and robust techniques for efficient refolding that ensure consistently high biological activity. Considerations for initiating development of protocols consistent with Current Good Manufacturing Practices (cGMPs) to produce biologically active chemokines suitable for use in clinical trials are also discussed. PMID:26921961

  20. Genome-Wide Association Study of Genetic Variants in LPS-Stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-α Cytokine Response in a Danish Cohort.

    Directory of Open Access Journals (Sweden)

    Margit Hørup Larsen

    Full Text Available Cytokine response plays a vital role in various human lipopolysaccharide (LPS infectious and inflammatory diseases. This study aimed to find genetic variants that might affect the levels of LPS-induced interleukin (IL-6, IL-8, IL-10, IL-1ra and tumor necrosis factor (TNF-α cytokine production.We performed an initial genome-wide association study using Affymetrix Human Mapping 500 K GeneChip® to screen 130 healthy individuals of Danish descent. The levels of IL-6, IL-8, IL-10, IL-1ra and TNF-α in 24-hour LPS-stimulated whole blood samples were compared within different genotypes. The 152 most significant SNPs were replicated using Illumina Golden Gate® GeneChip in an independent cohort of 186 Danish individuals. Next, 9 of the most statistical significant SNPs were replicated using PCR-based genotyping in an independent cohort of 400 Danish individuals. All results were analyzed in a combined study among the 716 Danish individuals.Only one marker of the 500 K Gene Chip in the discovery study showed a significant association with LPS-induced IL-1ra cytokine levels after Bonferroni correction (P<10(-7. However, this SNP was not associated with the IL-1ra cytokine levels in the replication dataset. No SNPs reached genome-wide significance for the five cytokine levels in the combined analysis of all three stages.The associations between the genetic variants and the LPS-induced IL-6, IL-8, IL-10, IL-1ra and TNF-α cytokine levels were not significant in the meta-analysis. This present study does not support a strong genetic effect of LPS-stimulated cytokine production; however, the potential for type II errors should be considered.

  1. Regulation of MMP-3 expression and secretion by the chemokine eotaxin-1 in human chondrocytes

    Directory of Open Access Journals (Sweden)

    Chao Pin-Zhir

    2011-11-01

    Full Text Available Abstract Background Osteoarthritis (OA is characterized by the degradation of articular cartilage, marked by the breakdown of matrix proteins. Studies demonstrated the involvement of chemokines in this process, and some may potentially serve as diagnostic markers and therapeutic targets; however, the underlying signal transductions are not well understood. Methods We investigated the effects of the CC chemokine eotaxin-1 (CCL11 on the matrix metalloproteinase (MMP expression and secretion in the human chondrocyte cell line SW1353 and primary chondrocytes. Results Eotaxin-1 significantly induced MMP-3 mRNA expression in a dose-dependent manner. Inhibitors of extracellular signal-regulated kinase (ERK and p38 kinase were able to repress eotaxin-1-induced MMP-3 expression. On the contrary, Rp-adenosine-3',5'-cyclic monophosphorothioate (Rp-cAMPs, a competitive cAMP antagonist for cAMP receptors, and H-89, a protein kinase A (PKA inhibitor, markedly enhanced eotaxin-1-induced MMP-3 expression. These results suggest that MMP-3 expression is specifically mediated by the G protein-coupled eotaxin-1 receptor activities. Interestingly, little amount of MMP-3 protein was detected in the cell lysates of eotaxin-1-treated SW1353 cells, and most of MMP-3 protein was in the culture media. Furthermore we found that the eotaxin-1-dependent MMP-3 protein secretion was regulated by phospholipase C (PLC-protein kinase C (PKC cascade and c-Jun N-terminal kinase (JNK/mitogen-activated protein (MAP kinase pathways. These data indicate a specific regulation of MMP-3 secretion also by eotaxin-1 receptor activities. Conclusions Eotaxin-1 not only induces MMP-3 gene expression but also promotes MMP-3 protein secretion through G protein-coupled eotaxin-1 receptor activities. Chemokines, such as eotaxin-1, could be a potential candidate in the diagnosis and treatment of arthritis.

  2. Cultures of human colonic epithelial cells isolated from endoscopical biopsies from patients with inflammatory bowel disease. Effect of IFNgamma, TNFalpha and IL-1beta on viability, butyrate oxidation and IL-8 secretion

    DEFF Research Database (Denmark)

    Pedersen, G; Saermark, T; Bendtzen, K;

    2000-01-01

    nontransformed colonic epithelial cells. We investigated the effects of TNFalpha, IFNgamma and IL-1beta on viability, short chain fatty acid (butyrate) oxidation and IL-8 secretion in human colonic epithelial cell cultures in vitro obtained from macroscopically normal mucosa from IBD patients and controls...... to TNFalpha + IFNgamma exposure (median 74%) compared to cells from controls (median 58 %) (P Butyrate oxidation, as measured by entrapment of 14CO2, was not inhibited in cells exposed to TNFalpha + IFNgamma, neither from controls (median 112%) nor from IBD patients (median 108%), suggesting...

  3. Selected immunological changes in patients with Goeckerman's therapy TNF-alpha, sE-selectin, sP-selectin, sICAM-1 and IL-8

    Energy Technology Data Exchange (ETDEWEB)

    Borska, L.; Fiala, Z.; Krejsek, J.; Andrys, C.; Vokurkova, D.; Hamakova, K.; Kremlacek, J.; Ettler, K. [Charles University, Hradec Kralove (Czech Republic). Faculty of Medicine

    2006-07-01

    Psoriasis is one of the most frequent inflammatory skin diseases in which abnormal individual immune reactivity plays an important role. The aim of the present study was to describe selected immunological changes, concerning pro-inflammatory cytokines (TNF-alpha, IL-8) and adhesion molecules (sE-selectin, sP-selectin, sICAM-1), in 56 patients cured by Goeckerman's therapy (GT). GT includes dermal application of crude coal tar (containing polycyclic aromatic hydrocarbons) and exposure to UV radiation.

  4. Differential Chemokine Signature between Human Preadipocytes and Adipocytes

    Science.gov (United States)

    Ignacio, Rosa Mistica C.; Gibbs, Carla R.; Lee, Eun-Sook

    2016-01-01

    Obesity is characterized as an accumulation of adipose tissue mass represented by chronic, low-grade inflammation. Obesity-derived inflammation involves chemokines as important regulators contributing to the pathophysiology of obesity-related diseases such as cardiovascular disease, diabetes and some cancers. The obesity-driven chemokine network is poorly understood. Here, we identified the profiles of chemokine signature between human preadipocytes and adipocytes, using PCR arrays and qRT-PCR. Both preadipocytes and adipocytes showed absent or low levels in chemokine receptors in spite of some changes. On the other hand, the chemokine levels of CCL2, CCL7-8, CCL11, CXCL1-3, CXCL6 and CXCL10-11 were dominantly expressed in preadipocytes compared to adipocytes. Interestingly, CXCL14 was the most dominant chemokine expressed in adipocytes compared to preadipocytes. Moreover, there is significantly higher protein level of CXCL14 in conditioned media from adipocytes. In addition, we analyzed the data of the chemokine signatures in adipocytes obtained from healthy lean and obese postmenopausal women based on Gene Expression Omnibus (GEO) dataset. Adipocytes from obese individuals had significantly higher levels in chemokine signature as follows: CCL2, CCL13, CCL18-19, CCL23, CCL26, CXCL1, CXCL3 and CXCL14, as compared to those from lean ones. Also, among the chemokine networks, CXCL14 appeared to be the highest levels in adipocytes from both lean and obese women. Taken together, these results identify CXCL14 as an important chemokine induced during adipogenesis, requiring further research elucidating its potential therapeutic benefits in obesity. PMID:27340388

  5. Differential Chemokine Signature between Human Preadipocytes and Adipocytes.

    Science.gov (United States)

    Ignacio, Rosa Mistica C; Gibbs, Carla R; Lee, Eun-Sook; Son, Deok-Soo

    2016-06-01

    Obesity is characterized as an accumulation of adipose tissue mass represented by chronic, low-grade inflammation. Obesity-derived inflammation involves chemokines as important regulators contributing to the pathophysiology of obesity-related diseases such as cardiovascular disease, diabetes and some cancers. The obesity-driven chemokine network is poorly understood. Here, we identified the profiles of chemokine signature between human preadipocytes and adipocytes, using PCR arrays and qRT-PCR. Both preadipocytes and adipocytes showed absent or low levels in chemokine receptors in spite of some changes. On the other hand, the chemokine levels of CCL2, CCL7-8, CCL11, CXCL1-3, CXCL6 and CXCL10-11 were dominantly expressed in preadipocytes compared to adipocytes. Interestingly, CXCL14 was the most dominant chemokine expressed in adipocytes compared to preadipocytes. Moreover, there is significantly higher protein level of CXCL14 in conditioned media from adipocytes. In addition, we analyzed the data of the chemokine signatures in adipocytes obtained from healthy lean and obese postmenopausal women based on Gene Expression Omnibus (GEO) dataset. Adipocytes from obese individuals had significantly higher levels in chemokine signature as follows: CCL2, CCL13, CCL18-19, CCL23, CCL26, CXCL1, CXCL3 and CXCL14, as compared to those from lean ones. Also, among the chemokine networks, CXCL14 appeared to be the highest levels in adipocytes from both lean and obese women. Taken together, these results identify CXCL14 as an important chemokine induced during adipogenesis, requiring further research elucidating its potential therapeutic benefits in obesity. PMID:27340388

  6. PPAR-γ Activation Inhibits Angiogenesis by Blocking ELR+CXC Chemokine Production in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Venkateshwar G. Keshamouni

    2005-03-01

    Full Text Available Activation of peroxisome proliferator-activated receptor-γ (PPAR-γ results in inhibition of tumor growth in various types of cancers, but the mechanism(s by which PPAR-γ induces growth arrest has not been completely defined. In a recent study, we demonstrated that treatment of A549 (human non small cell lung cancer cell line tumor-bearing SCID mice with PPAR-γ ligands troglitazone (Tro and pioglitazone significantly inhibits primary tumor growth. In this study, immunohistochemical analysis of Tro-treated and Pio-treated tumors with factor VIII antibody revealed a significant reduction in blood vessel density compared to tumors in control animals, suggesting inhibition of angiogenesis. Further analysis showed that treatment of A549 cells in vitro with Tro or transient transfection of A549 cells with constitutively active PPAR-γ (VP16-PPAR-γ construct blocked the production of the angiogenic ELR +CXC chemokines IL-8 (CXCL8, ENA-78 (CXCL5, Gro-α (CXCL1. Similarly, an inhibitor of NF-ΚB activation (PDTC also blocked CXCL8, CXCL5, CXCL1 production, consistent with their NF-ΚB-dependent regulation. Conditioned media from A549 cells induce human microvascular endothelial cell (HMVEC chemotaxis. However, conditioned media from Tro-treated A549 cells induced significantly less HMVEC chemotaxis compared to untreated A549 cells. Furthermore, PPAR-γ activation inhibited NF-ΚB transcriptional activity, as assessed by TransAM reporter gene assay. Collectively, our data suggest that PPAR-γ ligands can inhibit tumor-associated angiogenesis by blocking the production of ELR+CXC chemokines, which is mediated through antagonizing NF-ΚB activation. These antiangiogenic effects likely contribute to the inhibition of primary tumor growth by PPAR-γ ligands.

  7. The cytokine and chemokine profiles in patients with hand, foot and mouth disease of different severities in Shanghai, China, 2010.

    Directory of Open Access Journals (Sweden)

    Mei Zeng

    Full Text Available BACKGROUND AND PURPOSE: Systemic upregulation of inflammatory cytokines is characteristic of critical severe hand, foot, and mouth disease (HFMD with pulmonary edema. Thus, immunomodulatory medicines such as steroids, including methylprednisolone, have been proposed to treat patients with severe HFMD in China, because it is postulated that inflammatory cytokines play a role in the development of severe complications. This study is to further investigate the inflammatory response in the relatively mild HFMD patients, and whether steroid treatment has a beneficial effect on the suppression of inflammation in HFMD patients. METHOD: We measured the levels of 50 kinds of chemokines, cytokines, growth factors and soluble receptors in serum samples from control patients without HFMD and the HFMD patients with or without prior treatment of intravenous methylprednisolone. RESULTS: Our present study found that even relatively mild HFMD patients without central nervous system (CNS complications had elevated serum levels of inflammatory cytokines, including interleukin (IL-3, IL-6, IL-12p40, and tumor necrosis factor (TNF-α, which suggested systemic inflammation. In contrast, these patients also have decreased levels of other serum biomarkers, including IL-1Ra, IL-8, IL-16, soluble ICAM-1, CXCL-1, and CCL27. The dysregulation of cytokine and chemokine expression may be involved in CNS complications and unbalanced circulating leukocytes in HFMD patients. Surprisingly, patients treated with methylprednisolone had no difference in the expression levels of HFMD-associated biomarkers instead had slightly increased levels of IL-17A, which was not associated with the occurrence of HFMD. CONCLUSION: Whether steroid treatment has any beneficial effect on the prognosis of HFMD patients requires to be further investigated.

  8. CXCL12 chemokine and GABA neurotransmitter systems crosstalk and their putative roles

    Directory of Open Access Journals (Sweden)

    Guyon eAlice

    2014-04-01

    Full Text Available Since CXCL12 and its receptors, CXCR4 and CXCR7, have been found in the brain, the role of this chemokine has been expanded from chemoattractant in the immune system to neuromodulatory in the brain. Several pieces of evidence suggest that this chemokine system could crosstalk with the GABAergic system, known to be the main inhibitory neurotransmitter system in the brain. Indeed, GABA and CXCL12 as well as their receptors are colocalized in many cell types including neurons and there are several examples in which these two systems interact. Several mechanisms can be proposed to explain how these systems interact, including receptor-receptor interactions, crosstalk at the level of second messenger cascades, or direct pharmacological interactions, as GABA and GABAB receptor agonists/antagonists have been shown to be allosteric modulators of CXCR4.The interplay between CXCL12/CXCR4-CXCR7 and GABA/GABAA-GABAB receptors systems could have many physiological implications in neurotransmission, cancer and inflammation. In addition, the GABAB agonist baclofen is currently used in medicine to treat spasticity in patients with spinal cord injury, cerebral palsy, traumatic brain injury, multiple sclerosis and other disorders. More recently it has also been used in the treatment of alcohol dependence and withdrawal. The allosteric effects of this agent on CXCR4 could contribute to these beneficial effects or at the opposite, to its side effects.

  9. Differential expression of chemokines, chemokine receptors and proteinases by foreign body giant cells (FBGCs) and osteoclasts.

    Science.gov (United States)

    Khan, Usman A; Hashimi, Saeed M; Khan, Shershah; Quan, Jingjing; Bakr, Mahmoud M; Forwood, Mark R; Morrison, Nigel M

    2014-07-01

    Osteoclasts and foreign body giant cells (FBGCs) are both derived from the fusion of macropahges. These cells are seen in close proximity during foreign body reactions, therefore it was assumed that they might interact with each other. The aim was to identify important genes that are expressed by osteoclasts and FBGCs which can be used to understand peri-implantitis and predict the relationship of these cells during foreign body reactions. Bone marrow macrophages (BMM) were treated with receptor activator of nuclear factor kappa B ligand (RANKL) to produce osteoclasts. Quantitative PCR (qPCR) was used to identify the genes that were expressed by osteoclasts and FBGCs compared to macrophage controls. TRAP staining was used to visualise the cells while gelatine zymography and western blots were used for protein expression. Tartrate-resistant acid phosphatase (TRAP), matrix metallo proteinase 9 (MMP9), nuclear factor of activated T cells 1 (NFATc1), cathepsin K (CTSK) and RANK were significantly lower in FBGCs compared to osteoclasts. Inflammation specific chemokines such as monocyte chemotactic protein (MCP1 also called CCL2), macrophage inflammatory protein 1 alpha (MIP1α), MIP1β and MIP1γ, and their receptors CCR1, CCR3 and CCR5, were highly expressed by FBGCs. FBGCs were negative for osteoclast specific markers (RANK, NFATc1, CTSK). FBGCs expressed chemokines such as CCL2, 3, 5 and 9 while osteoclasts expressed the receptors for these chemokines i.e. CCR1, 2 and 3. Our findings show that osteoclast specific genes are not expressed by FBGCs and that FBGCs interact with osteoclasts during foreign body reaction through chemokines.

  10. Cascade Organic Solar Cells

    KAUST Repository

    Schlenker, Cody W.

    2011-09-27

    We demonstrate planar organic solar cells consisting of a series of complementary donor materials with cascading exciton energies, incorporated in the following structure: glass/indium-tin-oxide/donor cascade/C 60/bathocuproine/Al. Using a tetracene layer grown in a descending energy cascade on 5,6-diphenyl-tetracene and capped with 5,6,11,12-tetraphenyl- tetracene, where the accessibility of the π-system in each material is expected to influence the rate of parasitic carrier leakage and charge recombination at the donor/acceptor interface, we observe an increase in open circuit voltage (Voc) of approximately 40% (corresponding to a change of +200 mV) compared to that of a single tetracene donor. Little change is observed in other parameters such as fill factor and short circuit current density (FF = 0.50 ± 0.02 and Jsc = 2.55 ± 0.23 mA/cm2) compared to those of the control tetracene-C60 solar cells (FF = 0.54 ± 0.02 and Jsc = 2.86 ± 0.23 mA/cm2). We demonstrate that this cascade architecture is effective in reducing losses due to polaron pair recombination at donor-acceptor interfaces, while enhancing spectral coverage, resulting in a substantial increase in the power conversion efficiency for cascade organic photovoltaic cells compared to tetracene and pentacene based devices with a single donor layer. © 2011 American Chemical Society.

  11. Virally encoded chemokines and chemokine receptors in the role of viral infections

    DEFF Research Database (Denmark)

    Holst, Peter J; Lüttichau, Hans R; Schwartz, Thue W;

    2003-01-01

    Large DNA viruses such as pox- and in particular herpesviruses are notorious in their ability to evade the immune system and to be maintained in the general population. Based on the accumulated knowledge reviewed in this study it is evident that important mechanisms of these actions are the acqui......Large DNA viruses such as pox- and in particular herpesviruses are notorious in their ability to evade the immune system and to be maintained in the general population. Based on the accumulated knowledge reviewed in this study it is evident that important mechanisms of these actions...... are the acquisition and modification of host-encoded chemokines and chemokine receptors. The described viral molecules leave nothing to chance and have thoroughly and efficiently corrupted the host immune system. Through this process viruses have identified key molecules in antiviral responses by their inhibition...... for antiviral therapies have been provided by UL33, UL78 and in particular ORF74 and the chances are that many more will follow. In HHV8 vMIP-2 and the chemokine-binding proteins potent anti-inflammatory agents have been provided. These have already had their potential demonstrated in animal models and may...

  12. The Role of Chemokines in Breast Cancer Pathology and Its Possible Use as Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    M. Isabel Palacios-Arreola

    2014-01-01

    Full Text Available Chemokines are small proteins that primarily regulate the traffic of leukocytes under homeostatic conditions and during specific immune responses. The chemokine-chemokine receptor system comprises almost 50 chemokines and approximately 20 chemokine receptors; thus, there is no unique ligand for each receptor and the binding of different chemokines to the same receptor might have disparate effects. Complicating the system further, these effects depend on the cellular milieu. In cancer, although chemokines are associated primarily with the generation of a protumoral microenvironment and organ-directed metastasis, they also mediate other phenomena related to disease progression, such as angiogenesis and even chemoresistance. Therefore, the chemokine system is becoming a target in cancer therapeutics. We review the emerging data and correlations between chemokines/chemokine receptors and breast cancer, their implications in cancer progression, and possible therapeutic strategies that exploit the chemokine system.

  13. Comparisons of IL-8, ROS and p53 responses in human lung epithelial cells exposed to two extracts of PM2.5 collected from an e-waste recycling area, China

    International Nuclear Information System (INIS)

    To identify the different effects of organic-soluble and water-soluble pollutants adsorbed on PM2.5 (PM: particulate matter) released from e-waste (electrical/electronic waste) on inflammatory response, oxidative stress and DNA damage, interleukin-8 (IL-8), reactive oxygen species (ROS) and p53 protein levels were determined and compared in human lung epithelial A549 cells exposed to extracts of PM2.5 collected from two sampling sites in an e-waste recycling area in China. It is found that both extracts induced increases of IL-8 release, ROS production and p53 protein expression. The differences between the organic-soluble and water-soluble extracts were determined as of significance for ROS production (p < 0.05) and p53 protein expression (p < 0.01). The ROS production and p53 protein expression induced by the organic-soluble extracts were found to be greater than those induced by the water-soluble extracts, for both sampling sites. The results indicated that PM2.5 collected from the e-waste recycling areas could lead to inflammatory response, oxidative stress and DNA damage, and the organic-soluble extracts had higher potential to induce such adverse effects on human health.

  14. Genetic characterization of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18) with relevant biological roles in lagomorphs.

    Science.gov (United States)

    Neves, Fabiana; Abrantes, Joana; Almeida, Tereza; de Matos, Ana Lemos; Costa, Paulo P; Esteves, Pedro J

    2015-11-01

    ILs, as essential innate immune modulators, are involved in an array of biological processes. In the European rabbit (Oryctolagus cuniculus) IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18 have been implicated in inflammatory processes and in the immune response against rabbit hemorrhagic disease virus and myxoma virus infections. In this study we characterized these ILs in six Lagomorpha species (European rabbit, pygmy rabbit, two cottontail rabbit species, European brown hare and American pika). Overall, these ILs are conserved between lagomorphs, including in their exon/intron structure. Most differences were observed between leporids and American pika. Indeed, when comparing both, some relevant differences were observed in American pika, such as the location of the stop codon in IL-1α and IL-2, the existence of a different transcript in IL8 and the number of cysteine residues in IL-1β. Changes at N-glycosylation motifs were also detected in IL-1, IL-10, IL-12B and IL-15. IL-1α is the protein that presents the highest evolutionary distances, which is in contrast to IL-12A where the distances between lagomorphs are the lowest. For all these ILs, sequences of human and European rabbit are more closely related than between human and mouse or European rabbit and mouse. PMID:26395994

  15. Chemokine genetic polymorphism in human health and disease.

    Science.gov (United States)

    Qidwai, Tabish

    2016-08-01

    Chemokine receptor-ligand interaction regulates transmigration of lymphocytes and monocytes from circulation to the inflammatory sites. CC chemokine receptors, chemokine receptor 2(CCR2) and 5 (CCR5) are important in recruitment of immune cells as well as non-immune cells under pathological condition. CCR2, CCR5 and their ligands (CCL2 and CCL5) are major contributor to the autoimmune and inflammatory diseases and cancer. Currently studies are being done to explore genetic variations in chemokine genes and their involvement in diseases that could make clear disease severity and deaths. Conflicting results of studies in different populations and diseases promoted to investigate chemokines genetic polymorphisms in miscellaneous diseases. This study is aimed to evaluate the influence of chemokines genetic polymorphisms in pathogenesis and outcome of prevalent non infectious diseases. Present study demonstrates the likely role played by genetic variations in drug response and evolution. Moreover this study highlights chemokine as therapeutic target and diagnostic biomarker in pathological condition. PMID:27262929

  16. Inhibition of Epithelial CC-Family Chemokine Synthesis by the Synthetic Chalcone DMPF-1 via Disruption of NF-κB Nuclear Translocation and Suppression of Experimental Asthma in Mice

    Directory of Open Access Journals (Sweden)

    Revathee Rajajendram

    2015-01-01

    Full Text Available Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The interaction between airway epithelium and inflammatory mediators plays a key role in the pathogenesis of asthma. In vitro studies evaluated the inhibitory effects of 3-(2,5-dimethoxyphenyl-1-(5-methylfuran-2-ylprop-2-en-1-one (DMPF-1, a synthetic chalcone analogue, upon inflammation in the A549 lung epithelial cell line. DMPF-1 selectively inhibited TNF-α-stimulated CC chemokine secretion (RANTES, eotaxin-1, and MCP-1 without any effect upon CXC chemokine (GRO-α and IL-8 secretion. Western blot analysis further demonstrated that the inhibitory activity resulted from disruption of p65NF-κB nuclear translocation without any effects on the mitogen-activated protein kinase (MAPK pathway. Treatment of ovalbumin-sensitized and ovalbumin-challenged BALB/c mice with DMPF-1 (0.2–100 mg/kg demonstrated significant reduction in the secretion and gene expression of CC chemokines (RANTES, eotaxin-1, and MCP-1 and Th2 cytokines (IL-4, IL-5, and IL-13. Furthermore, DMPF-1 treatment inhibited eosinophilia, goblet cell hyperplasia, peripheral blood total IgE, and airway hyperresponsiveness in ovalbumin-sensitized and ovalbumin-challenged mice. In conclusion, these findings demonstrate the potential of DMPF-1, a nonsteroidal compound, as an antiasthmatic agent for further pharmacological evaluation.

  17. Chemokines and Chemokine Receptors as Novel Therapeutic Targets in Rheumatoid Arthritis (RA): Inhibitory Effects of Traditional Chinese Medicinal Components

    Institute of Scientific and Technical Information of China (English)

    XinChen; JoostJ.Oppenheim; O.M.ZackHoward

    2004-01-01

    Chemokines belong to a large family of inflammatory cytokines responsible for migration and accumulation of leukocytes at inflammatory sites. Over the past decade, accumulating evidence indicated a crucial role for chemokines and chemokine receptors in the pathophysiology of rheumatoid arthritis (RA). RA is a chronic autoimmune disease in which the synovial tissue is heavily infiltrated by leukocytes. Chemokines play an important role in the infiltration, localization, retention of infiltrating leukocytes and generation of ectopic germinal centers in the inflamed synovium. Recent evidence also suggests that identification of inhibitors directly targeting chemokines or their receptors may provide a novel therapeutic strategy in RA. Traditional Chinese medicinals (TCMs) have a long history in the treatment of inflammatory joint disease. The basis forthe clinical benefits of TCM remains largely unclear. Our studies have led to the identification of numerousnovel chemokine/chemokine receptor inhibitors present in anti,inflammatory TCMs. All of these inhibitors were previously reported by other researchers to have anti-arthritic effect, which may be attributable, at leastin part, to their inhibitory effect on chemokine and/or chemokine receptor. Therefore, identification of agents capable of targeting chemokine/chemokine receptor interactions has suggested a mechanism of action for several TCM components and provided a means of identifying additional anti-RA TCM. Thus, this approach may lead to the discovery of new inhibitors of chemokines or chemokine receptors that can be used to treat diseases associated with inappropriately overactive chemokine mediated inflammatory reactions. Cellular & Molecular Immunology. 2004;1(5):336-342.

  18. Effects of continuous positive airway pressure on expressions of IL-1β and IL-8 mRNA in alveolar lavage cells of old patients with lung tumor during one-lung ventilation%持续气道正压对高龄肺癌患者单肺通气中肺泡灌洗细胞IL-1β和IL-8mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    张光明; 钱刚; 朱明

    2011-01-01

    目的 观察持续气道正压(continuous positive airway pressure,CPAP)对高龄肺癌患者单肺通气(one-lung ventilation,OLV)中非通气侧肺泡灌洗细胞IL-1β和IL-8 mRNA的表达,在分子水平上探讨CPAP对肺炎性反应的影响.方法 选择单肺通气下年龄>65岁的肺癌开胸手术患者28例,ASA Ⅰ~Ⅱ级,随机分为对照组(n=14)和CPAP组(n=14).对照组在麻醉期间非通气侧肺的支气管导管直接开口于大气中,CPAP组麻醉期间非通气侧肺持续给予CPAP(压力3~5 cmH2O,1 cmH2O=1.02 Pa).在单肺通气开始和通气2 h后分别对两组患者非通气侧肺用纤维支气管镜行支气管肺泡灌洗(bronchoalveolar lavage,BAL),从灌洗液中收获细胞提取RNA,逆转录合成cDNA,以β-actin为内标准作PCR后电泳扫描求积,检测肺泡灌洗细胞IL-1β和IL-8 mRNA的表达.结果 单肺通气2 h后,对照组比CPAP组非通气侧肺肺泡灌洗液中IL-8和IL-1β mRNA的表达显著增加(P<0.01).结论 单肺通气中非通气侧肺给予适度的CPAP可以有效减少高龄肺癌患者肺泡灌洗细胞促炎性细胞因子mRNA的表达水平,抑制肺局部炎症反应,对非通气侧肺可能有一定的保护作用.%Objective To investigate the effects of continuous positive airway pressure (CPAP) on the expression of IL-1β and IL-8 mRNA in alveolar lavage cells of old patients with lung tumor during onelung ventilation (OLV). Methods Twenty-eight patients with lung tumor, ASA Ⅰ - Ⅱ, aged above 65 years old who underwent lobectomy were randomly divided into CPAP group ( n = 14) and control group (n = 14). There was no ventilation on the non-ventilated lung which was opened to the air in control group. Oxygen was administered via CPAP (Pressure 3 - 5 cmH2 O, 1 cmH2O = 1.02 Pa) system to the non-ventilated lung during OLV in CPAP group. Alveolar lavage cells were harvested by bronchoalveolar lavage at the beginning of OLV and 2 hours after OLV. RNA was extracted from the harvested

  19. Cascaded Poisson processes

    Science.gov (United States)

    Matsuo, Kuniaki; Saleh, Bahaa E. A.; Teich, Malvin Carl

    1982-12-01

    We investigate the counting statistics for stationary and nonstationary cascaded Poisson processes. A simple equation is obtained for the variance-to-mean ratio in the limit of long counting times. Explicit expressions for the forward-recurrence and inter-event-time probability density functions are also obtained. The results are expected to be of use in a number of areas of physics.

  20. CSS - Cascading Style Sheets

    OpenAIRE

    Martinelli, Massimo

    2009-01-01

    Curso "CSS - Cascading Style Sheets" sobre programación web con CSS para el "Máster doble competencia en ciencias informáticas y ciencias sociales" ("Master double competence in computer science and social science"). Proyecto TEMPUS JEP – 26235-2005

  1. Integrated Broadband Quantum Cascade Laser

    Science.gov (United States)

    Mansour, Kamjou (Inventor); Soibel, Alexander (Inventor)

    2016-01-01

    A broadband, integrated quantum cascade laser is disclosed, comprising ridge waveguide quantum cascade lasers formed by applying standard semiconductor process techniques to a monolithic structure of alternating layers of claddings and active region layers. The resulting ridge waveguide quantum cascade lasers may be individually controlled by independent voltage potentials, resulting in control of the overall spectrum of the integrated quantum cascade laser source. Other embodiments are described and claimed.

  2. MiR-100-3p and miR-877-3p regulate overproduction of IL-8 and IL-1β in mesangial cells activated by secretory IgA from IgA nephropathy patients.

    Science.gov (United States)

    Liang, Yan; Zhao, Guoqiang; Tang, Lin; Zhang, Junjun; Li, Tianfang; Liu, Zhangsuo

    2016-10-01

    IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis, characterized by mesangial deposition of pathogenic IgA and the injury to mesangial cells. Our previous studies indicate that secretory IgA (SIgA) plays an important role in the pathogenesis of IgAN, and miR-16 is involved in destructive process in mesangial cells mediated by the SIgA from IgAN patients. Our current study aimed to study the role of miRNAs in the effect of SIgA from IgAN patients on mesangial cells. MicroRNA microarray and cytokines assay were performed to obtain the differential microRNAs expression profile in human renal mesangial cells stimulated by SIgA from IgAN patients (P-SIgA) with the cells treated by SIgA from healthy subjects (N-SgA) as control. The microRNAs with the most significant differences in microarray analysis were validated by quantitative RT-PCR. Among them, miR-100-3p and miR-877-3p were selected to predict target gene related to cytokines detecting in this study. Fifty-six differentially expressed microRNAs were chosen and 17 microRNAs with the most prominent changes were validated. Compared with N-SIgA, P-SIgA increased the production of interleukin (IL)-1β, IL-8, monocyte chemotactic protein-1 and transforming growth factor-β1. In addition, we for the first time demonstrated that over-production of IL-8 induced by the SIgA was regulated by down-expression of miR-100-3p in mesangial cells. Similarly, IL-1β over-production was regulated by down-expression of miR-877-3p. Our findings represent a pathogenic microRNAs expression profiling in human mesangial cells activated by P-SIgA. Furthermore, we provide a new explanation characterizing the molecular mechanism responsible for the regulation of IL-1β and IL-8 production in P-SIgA-triggered mesangial cells.

  3. Changes and clinical significance of IL-8,sP-selectin in the patients with acute traumatic brain injury%急性颅脑损伤患者血清白细胞介素-8和可溶性P-选择素的变化及临床意义

    Institute of Scientific and Technical Information of China (English)

    冯杰; 杨晓明; 冯贵龙; 张辉; 路长宇; 边艳峰

    2011-01-01

    Objective To study the changes of serum IL -8, sP - selectin and their clinical significance in the patients with acute traumatic brain injury (TBI). Methods The serum levels of IL- 8 and sP - selectin from 60 patients with TBI were measured at different times after injury by ELISA, then the correlation analysis among the serum levels of IL - 8, sP - selectin and GCS scores after injury was conducted and were compared with the control group. Results The serum levels of IL -8, sP - selectin in the patients with acute TBI were significantly higher than those in the control group on the 24 h, 3rd, 5th day after acute TBI ( P < 0.05 ). The serum levels of IL - 8 was still significantly higher than those in the control group on the 7th days after TBI (P < 0.05). The serum levels of sP -selectin and IL - 8 after injury were negatively correlated with GCS scores in TBI group( P < 0.01 ). The serum levels of sP - selectin were positively correlated with IL - 8 after injury( P < 0.05 ). Conclusion IL - 8 and sP - selectin were involved in the pathological process of acute TBI. Determination of their serum levels was of clinical importance in the evaluation of injury severity and prognosis.%目的 探讨急性颅脑损伤(TBI)后血清中白细胞介素-8(IL-8)和可溶性P-选择素(sP-selectin)的水平变化及其临床意义.方法 采用ELISA法检测60例急性颅脑损伤患者不同时间血清IL-8、sP-selectin含量,按GCS评分分组并与对照组比较,进行统计学分析.结果 急性颅脑损伤患者组IL-8、sP-selectin在发病后24 h、3 d和5 d的血清水平显著高于对照组(P<0.05),IL-8在发病后第7天仍显著高于对照组(P<0.05).发病后血清IL-8、sP-selectin水平与入院时GCS评分呈负相关(P<0.01).IL-8和sP-selectin两者在疾病的过程中呈正相关(P<0.05).结论 IL-8、sP-selectin共同参与了急性颅脑损伤的病理生理过程,其测定对评估脑损伤的严重程度和预后有重要的临床意义.

  4. Chemokines and inflammation in heart disease: adaptive or maladaptive?

    OpenAIRE

    Tarzami, Sima T.

    2011-01-01

    Heart disease is not only the leading cause of death, disability, and healthcare expense in the US, but also the leading cause of death worldwide. Therefore, treatments to lessen ischemia-related cardiac damage could affect a broad swath of the population and have significant health and fiscal impacts. Cardiac dysfunction has been associated with elevated circulating chemokine levels, both in animals and humans. Most studies in this area have focused on chemokine expression as a prominent fea...

  5. A new cascadic multigrid

    Institute of Scientific and Technical Information of China (English)

    SHI; Zhongci

    2001-01-01

    [1]Bornemann, F., Deuflhard, P., The cascadic multigrid method for elliptic problems, Numer. Math., 996, 75: 35.[2]Bornemann, F., Deuflhard, P., The cascadic multigrid method, The Eighth International Conference on Domain Decomposition Methods for Partial Differential Equations (eds. Glowinski, R., Periaux, J., Shi, Z. et al.), New York: John Wiley and Sons, 997.[3]Bornemann, F., Krause, R., Classical and cascadic multigrid-methodogical comparison, Proceedings of the 9th International Conference on Domain Decomposition (eds. Bjorstad, P., Espedal, M., Keyes, D.), New York: John Wiley and Sons, 998.[4]Shaidurov, V., Some estimates of the rate of convergence for the cascadic conjugate gradient method, Comp. Math. Applic., 996, 3: 6.[5]Shi, Z., Xu, X., Cascadic multigrid method for the second order elliptic problem, East-West J. Numer. Math., 998, 6: 309.[6]Shi, Z., Xu, X., Cascadic multigrid for elliptic problems, East-West J. Numer. Math., 999, 7: 99.[7]Shi, Z., Xu, X., Cascadic multigrid method for the plate bending problem, East-West J. Numer. Math., 998, 6: 37.[8]Braess, D., Dahmen, W., A cascade multigrid algorithm for the Stokes equations, Number. Math., 999, 82: 79.[9]Shi, Z., Xu, X., Cascadic multigrid for parabolic problems, J. Comput. Math., 2000, 8: 450.[10]Ciarlet, P.,The Finite Element Method for Elliptic Problems, Amsterdam: North-Holland, 978.[11]Zienkiewicz, O. C., The Finite Element Method, 3rd. ed., London: McGraw-Hill, 977.[12]Powell, M. J. D., Sabin, M. A., Piecewise quadratic approximations on triangles, ACM Trans. Mat. Software, 977, 3: 36.[13]Xu, J., The auxiliary space method and optimal multigrid precondition techniques for unstructured grids, Computing, 996, 56: 25.[14]Bank, R., Dupont, T., An optimal order process for solving finite element equations, Math. Comput., 980, 36: 35.[15]Brenner, S., Convergence of nonconforming multigrid methods without full elliptic regularity, Math

  6. Emerging Concepts and Approaches for Chemokine-Receptor Drug Discovery

    Science.gov (United States)

    O’Hayre, Morgan; Salanga, Catherina L.; Handel, Tracy M.; Hamel, Damon J.

    2010-01-01

    Importance of the field Chemokine receptors are G protein-coupled receptors (GPCRs) most noted for their role in cell migration. However, inappropriate utilization or regulation of these receptors is implicated in many inflammatory diseases, cancer and HIV, making them important drug targets. Areas covered in this review Allostery, oligomerization, and ligand bias are presented as they pertain to chemokine receptors and their associated pathologies. Specific examples of each are described from the recent literature and their implications are discussed in terms of drug discovery efforts targeting chemokine receptors. What the reader will gain Insight into the expanding view of the multitude of pharmacological variables that need to be considered or that may be exploited in chemokine receptor drug discovery. Take home message Since 2007, two drugs targeting chemokine receptors have been approved by the FDA, Maraviroc for preventing HIV infection and Mozobil™ for hematopoietic stem cell mobilization. While these successes permit optimism for chemokine receptors as drug targets, only recently has the complexity of this system begun to be appreciated. The concepts of allosteric inhibitors, biased ligands and functional selectivity raise the possibility that drugs with precisely-defined properties can be developed. Other complexities such as receptor oligomerization and tissue-specific functional states of receptors also offer opportunities for increased target and response specificity, although it will be more challenging to translate these ideas into approved therapeutics compared to traditional approaches. PMID:21132095

  7. Cultures of human colonic epithelial cells isolated from endoscopical biopsies from patients with inflammatory bowel disease. Effect of IFNgamma, TNFalpha and IL-1beta on viability, butyrate oxidation and IL-8 secretion

    DEFF Research Database (Denmark)

    Pedersen, G; Saermark, T; Bendtzen, K;

    2000-01-01

    nontransformed colonic epithelial cells. We investigated the effects of TNFalpha, IFNgamma and IL-1beta on viability, short chain fatty acid (butyrate) oxidation and IL-8 secretion in human colonic epithelial cell cultures in vitro obtained from macroscopically normal mucosa from IBD patients and controls....... Colonic crypts were isolated from endoscopical biopsies by ultra-short (10 min) EDTA/EGTA treatment, and exposed to TNFalpha, IFNgamma and IL-1beta for 24 hours. The combination of TNFalpha+IFNgamma induced a significant decrease in cell viability as judged by methyltetrazoleum (MTT) metabolism which...... decreased to median 68% of unexposed cultures (P beta had no significant effect. Cells from IBD patients were significantly less sensitive...

  8. Duffy antigen receptor for chemokines mediates chemokine endocytosis through a macropinocytosis-like process in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Yani Zhao

    Full Text Available The Duffy antigen receptor for chemokines (DARC shows high affinity binding to multiple inflammatory CC and CXC chemokines and is expressed by erythrocytes and endothelial cells. Recent evidence suggests that endothelial DARC facilitates chemokine transcytosis to promote neutrophil recruitment. However, the mechanism of chemokine endocytosis by DARC remains unclear.We investigated the role of several endocytic pathways in DARC-mediated ligand internalization. Here we report that, although DARC co-localizes with caveolin-1 in endothelial cells, caveolin-1 is dispensable for DARC-mediated (125I-CXCL1 endocytosis as knockdown of caveolin-1 failed to inhibit ligand internalization. (125I-CXCL1 endocytosis by DARC was also independent of clathrin and flotillin-1 but required cholesterol and was, in part, inhibited by silencing Dynamin II expression.(125I-CXCL1 endocytosis was inhibited by amiloride, cytochalasin D, and the PKC inhibitor Gö6976 whereas Platelet Derived Growth Factor (PDGF enhanced ligand internalization through DARC. The majority of DARC-ligand interactions occurred on the endothelial surface, with DARC identified along plasma membrane extensions with the appearance of ruffles, supporting the concept that DARC provides a high affinity scaffolding function for surface retention of chemokines on endothelial cells.These results show DARC-mediated chemokine endocytosis occurs through a macropinocytosis-like process in endothelial cells and caveolin-1 is dispensable for CXCL1 internalization.

  9. Quantum Cascade Detectors

    OpenAIRE

    Giorgetta, Fabrizio R.; Baumann, Esther; Graf, Marcel; Yang, Quankui; Manz, Christian; Köhler, Klaus; Beere, Harvey E.; Ritchie, David A.; Linfield, Edmund; Davies, Alexander G.; Fedoryshyn, Yuriy; Jackel, Heinz; Fischer, Milan; Faist, Jérôme; Hofstetter, Daniel

    2010-01-01

    This paper gives an overview on the design, fabrication, and characterization of quantum cascade detectors. They are tailorable infrared photodetectors based on intersubband transitions in semiconductor quantum wells that do not require an external bias voltage due to their asymmetric conduction band profile. They thus profit from favorable noise behavior, reduced thermal load, and simpler readout circuits. This was demonstrated at wavelengths from the near infrared at 2 μm to THz radiation a...

  10. Information cascade on networks

    Science.gov (United States)

    Hisakado, Masato; Mori, Shintaro

    2016-05-01

    In this paper, we discuss a voting model by considering three different kinds of networks: a random graph, the Barabási-Albert (BA) model, and a fitness model. A voting model represents the way in which public perceptions are conveyed to voters. Our voting model is constructed by using two types of voters-herders and independents-and two candidates. Independents conduct voting based on their fundamental values; on the other hand, herders base their voting on the number of previous votes. Hence, herders vote for the majority candidates and obtain information relating to previous votes from their networks. We discuss the difference between the phases on which the networks depend. Two kinds of phase transitions, an information cascade transition and a super-normal transition, were identified. The first of these is a transition between a state in which most voters make the correct choices and a state in which most of them are wrong. The second is a transition of convergence speed. The information cascade transition prevails when herder effects are stronger than the super-normal transition. In the BA and fitness models, the critical point of the information cascade transition is the same as that of the random network model. However, the critical point of the super-normal transition disappears when these two models are used. In conclusion, the influence of networks is shown to only affect the convergence speed and not the information cascade transition. We are therefore able to conclude that the influence of hubs on voters' perceptions is limited.

  11. Cytokine and chemokine mRNA expression profiles in BALF cells isolated from pigs single infected or co-infected with swine influenza virus and Bordetella bronchiseptica.

    Science.gov (United States)

    Kowalczyk, Andrzej; Pomorska-Mól, Małgorzata; Kwit, Krzysztof; Pejsak, Zygmunt; Rachubik, Jarosław; Markowska-Daniel, Iwona

    2014-06-01

    Pigs serve as a valuable animal experimental model for several respiratory pathogens, including Swine Influenza Virus (SIV) and Bordetella bronchiseptica (Bbr). To investigate the effect of SIV and Bbr coinfection on cytokine and viral RNA expression, we performed a study in which pigs were inoculated with SIV, Bbr or both pathogens (SIV/Bbr). Our results indicate that Bbr infection alters SIV clearance. Pulmonary lesions in the SIV/Bbr group were more severe when compared to SIV or Bbr groups and Bbr did not cause significant lesions. Broncho-alveolar lavage fluid (BALF) was examined for inflammatory mediators by qPCR. Interferon (IFN)-α, interleukin IL-8, IL-1 peaked in BALF at 2 DPI, while the virus titres and severity of clinical signs were maximal at the same time. Despite its increased expression in co-infected pigs, interferon-α did not enhance SIV clearance, since the viral replication was detected at the same day as the highest IFN levels. The mRNA levels for IFN-α, IL-1β and IL-8 were significantly higher in BALF of co-infected pigs and correlated with enhanced viral RNA titers in lungs, trachea and nasal swabs. Transcription of mRNA for IL-1β was stable in SIV and SIV/Bbr groups throughout all the study. In Bbr group, the levels of mRNAs for IL-1β were significantly higher at 2, 4 and 9 DPI. The mean levels of mRNAs for TNF-α were lower than the levels of other chemokines and cytokines in all infected groups. Transcript levels of IL-10 and IL-4 did not increase at each time points. Overall, SIV replication was increased by Bbr presence and the enhanced production of pro-inflammatory mediators could contribute to the exacerbated pulmonary lesions.

  12. Chemokine-Like Factor 1 (CKLF-1) is Overexpressed in Keloid Patients: A Potential Indicating Factor for Keloid-Predisposed Individuals.

    Science.gov (United States)

    Zhang, Mingzi; Xu, Ying; Liu, Yifang; Cheng, Yingying; Zhao, Pengxiang; Liu, Hao; Wang, Youbin; Ma, Xuemei

    2016-03-01

    Chemokine-like factor 1 (CKLF-1) is a novel cytokine which have a crucial role in immune and inflammatory responses. In this study, the expression level of CKLF-1 was measured to assess the difference between keloid patients and people without keloid. Fifty samples were taken from 30 patients: 10 keloid patients; 10 scar patients; and 10 patients without obvious scarring. Patients were randomly selected from the hospitalized patients of Peking Union Medical College Hospital from September 2013 to July 2015. Five groups of samples were established: keloid samples from keloid patients (K); normal skin samples from keloid patients (KS); scar samples from scar patients (C); normal skin samples from scar patients (CS); and normal skin samples from patients without obvious scarring (S). Hematoxylin and eosin (H&E) staining was used to observe morphological changes. CKLF-1, IL-6, IL-8, IL-18, and TGF-β were detected by immunohistochemical and western blot technology. The expression of CKLF-1's mRNA was also measured by the real-time quantitative polymerase chain reaction (RT-qPCR). Compared to the K group, the other 4 groups presented significantly less inflammatory infiltration and lower expression levels of CKLF-1, IL-6, IL-8, IL-18, and TGF-β. Among the 3 normal skin groups, the expression level of CKLF-1 was significantly higher in the KS group than in the CS or S group. The mRNA expression was also obvious in the K and KS groups. CKLF-1 and other inflammatory factors were overexpressed in the samples from keloid patients, indicating that the formation of keloid may be related to inflammation and that CKLF-1 may play an important role in this process. PMID:26986142

  13. Biased and G protein-independent signaling of chemokine receptors

    Directory of Open Access Journals (Sweden)

    Anne eSteen

    2014-06-01

    Full Text Available Biased signaling or functional selectivity occurs when a 7TM receptor preferentially activates one of several available pathways. It can be divided into three distinct forms: ligand bias, receptor bias, and tissue or cell bias, where it is mediated by different ligands (on the same receptor, different receptors (with the same ligand or different tissues or cells (for the same ligand-receptor pair. Most often biased signaling is differentiated into G protein-dependent and β-arrestin-dependent signaling. Yet, it may also cover signaling differences within these groups. Moreover, it may not be absolute, i.e. full versus no activation. Here we discuss biased signaling in the chemokine system, including the structural basis for biased signaling in chemokine receptors, as well as in class A 7TM receptors in general. This includes overall helical movements and the contributions of micro-switches based on recently published 7TM crystals and molecular dynamics studies. All three forms of biased signaling are abundant in the chemokine system. This challenges our understanding of classic redundancy inevitably ascribed to this system, where multiple chemokines bind to the same receptor and where a single chemokine may bind to several receptors – in both cases with the same functional outcome. The ubiquitous biased signaling confer a hitherto unknown specificity to the chemokine system with a complex interaction pattern that is better described as promiscuous with context-defined roles and different functional outcomes in a ligand-, receptor- or cell/tissue-defined manner. As the low number of successful drug development plans implies, there are great difficulties in targeting chemokine receptors; in particular with regard to receptor antagonists as anti-inflammatory drugs. Un-defined and putative non-selective targeting of the complete cellular signaling system could be the underlying cause of lack of success. Therefore, biased ligands could be the

  14. Measurement and clinical significance of IL-8 、IL-13 and IL-18 in serum of patients with bronchial asthma%支气管哮喘患者血清白细胞介素8、13、18水平的变化及意义

    Institute of Scientific and Technical Information of China (English)

    李富强

    2012-01-01

    Objective To investigate the change and significance of IL-8,IL-13 and IL-18 level in serum of patients with bronchial asthma.Methods 45 patients with acute exacerbation of bronchial asthma were selected (acute group),and remission group 45 patients and 30 healthy persons (control group) were selected.The serum IL-8,IL-13 and IL-18 levels were measured respectively by ELISA.Results The serum IL-8,IL-13 and IL-18 levels in acute group were significantly higher than that in control group and remission group ( t =5.21,5.13,4.99,5.32,5.48,5.59,P < 0.05 ) ; The serum IL-8,IL-13 and IL-18 levels in remission group were significantly higher than that in control group(t =4.18,4.71,4.89,P <0.05).Conclusion The levels of serum IL-8,IL-13 and IL-18 may be related to the severity of asthma attack.IL-8,IL-13 and IL-18 played important role in both pathogenesis and determination of asthma.%目的 探讨支气管哮喘患者血清白细胞介素8、13、18(IL-8、IL-13、IL-18)含量的变化及临床意义.方法 选择45例支气管哮喘急性发作期患者(急性发作期组)和45例缓解期患者(缓解期组),采用双抗体夹心ELISA法进行血清IL-8、IL-13和IL-18水平测定,另外选择30例健康体检者作为对照组,并进行统计学比较.结果 急性发作期组和缓解期组患者血清IL-8、IL-13和IL-18水平均明显高于对照组(t=5.21,5.13,4.99,5.32,5.48,5.59,均P<0.05);急性发作期组患者血清IL-8、IL-13和IL-18水平均明显高于缓解期组患者(t=4.18,4.71,4.89,均P<0.05).结论 IL-8、IL-13和IL-18可能参与了支气管哮喘的发病机制,支气管哮喘气道炎症可能与IL-8、IL-13和IL-18的上调有关.检测血清IL-8、IL-13和IL-18水平的变化对了解病情进展及指导用药具有十分重要的临床价值.

  15. Diverging mechanisms of activation of chemokine receptors revealed by novel chemokine agonists.

    Directory of Open Access Journals (Sweden)

    Jose Sarmiento

    Full Text Available CXCL8/interleukin-8 is a pro-inflammatory chemokine that triggers pleiotropic responses, including inflammation, angiogenesis, wound healing and tumorigenesis. We engineered the first selective CXCR1 agonists on the basis of residue substitutions in the conserved ELR triad and CXC motif of CXCL8. Our data reveal that the molecular mechanisms of activation of CXCR1 and CXCR2 are distinct: the N-loop of CXCL8 is the major determinant for CXCR1 activation, whereas the N-terminus of CXCL8 (ELR and CXC is essential for CXCR2 activation. We also found that activation of CXCR1 cross-desensitized CXCR2 responses in human neutrophils co-expressing both receptors, indicating that these novel CXCR1 agonists represent a new class of anti-inflammatory agents. Further, these selective CXCR1 agonists will aid at elucidating the functional significance of CXCR1 in vivo under pathophysiological conditions.

  16. Cytokines, Chemokines, and Chemokine Receptors Quantitative Expressions in Patients with Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Somayeh Rezaeifard

    2015-05-01

    Full Text Available Background: Cytokines, chemokines, and chemokine receptors regulate the proliferation and survival of tumor cells, angiogenesis, and metastasis to other organs. This network of ligands and receptors has been used in molecular targeting of cancer. Methods: We compared the mRNA expression of CXCR3, CXCL-10, CXCR4, CXCL-12, IL-4, and IL-10 in tissues of benign and malignant ovarian tumors by qRT-PCR method and evaluated serum IL-10 and CA-125 content of these patients by ELISA during one year. Results: Our result showed a trend toward a higher expression of CXCR4 in malignant ovarian tissues compared with the benign ovarian cysts (P>0.05. However, SDF-1, IP-10, IL-4, CXCR3, and IL-10 had a lower trend in mRNA expression in malignant ovarian tissues compared to the benign cyst tissues. Except for IL-4 (P=0.01 and SDF-1 (P=0.02, the data for other factors were not statistically significant. A trend toward higher concentration of IL-10 was observed in the serum of ovarian cancer patients compared to those with benign cysts; however, the difference was not significant. CA-125 concentration in the serum of ovarian cancer patients was higher than that of benign cyst patients (P=0.05. Conclusion: According to results obtained, we hypothesize that the lower expression of SDF-1 in malignant tissues may have an important role in ovarian tumor growth. However, this hypothesis requires more investigation. Higher levels of CA125 and IL-10 in the serum of patients might indicate that the combination of these biomarkers could be used for distinguishing patients with ovarian cancer from those with benign cysts.

  17. Polymorphisms in chemokine and chemokine receptor genes and the development of coal workers' pneumoconiosis

    Energy Technology Data Exchange (ETDEWEB)

    Nadif, R.; Mintz, M.; Rivas-Fuentes, S.; Jedlicka, A.; Lavergne, E.; Rodero, M.; Kauffmann, F.; Combadiere, C.; Kleeberger, S.R. [INSERM, Villejuif (France)

    2006-02-07

    Chemokines and their receptors are key regulators of inflammation and may participate in the lung fibrotic process. Associations of polymorphisms in CCL5 (G-403A) and its receptor CCR5 {Delta}32), CCL2 (A-2578G) and CCR2 (V641), and CX3CR1 V2491 and T280M with coal worker's pneumoconiosis (CWP) were investigated in 209 miners examined in 1990, 1994 and 1999. Coal dust exposure was assessed by job history and ambient measures. The main health outcome was lung computed tomography (CT) score in 1990. Internal coherence was assessed by studying CT score in 1994, 4-year change in CT score, and CWP prevalence in 1999. CCR5 {Delta}32 carriers had significantly higher CT score in 1990 and 1994 (2.15 vs. 1.28, p = 0.01; 3.04 vs. 1.80, p = 0.04). The CX3CR1 1249 allele was significantly associated with lower 1990 CT score and lower progression in 4-year change in CT score in CCR5{Delta}32 carriers only (p for interaction = 0.03 and 0.02). CX3CR1 V2491 was associated with lower 1999 CWP prevalence (16.7%, 13.2%, 0.0% for VV, VI and II); the effect was most evident in miners with high dust exposure (31.6%, 21.7%, 0.0%). Our findings indicate that chemokine receptors CCR5 and CX3CR1 may be involved in the development of pneumoconiosis.

  18. Multiphase cascaded lattice Boltzmann method

    OpenAIRE

    Lycett-Brown, D.; Luo, K. H.

    2014-01-01

    To improve the stability of the lattice Boltzmann method (LBM) at high Reynolds number the cascaded LBM has recently been introduced. As in the multiple relaxation time (MRT) method the cascaded LBM introduces additional relaxation times into the collision operator, but does so in a co-moving reference frame. This has been shown to significantly increase stability at low viscosity in the single phase case. Here the cascaded LBM is further developed to include multiphase flow. For this the for...

  19. Cascade hydrodewaxing process

    Energy Technology Data Exchange (ETDEWEB)

    Yen, J.H.

    1986-07-08

    A cascade catalytic hydrodewaxing process is described comprising: (a) passing a hydrocarbon feedstock containing waxy components selected from a group of normal paraffins and slightly branched chain paraffins over a hydroisomerization catalyst comprising a crystalline silicate zeolite having the structure of ZSM-12 in admixture with a crystalline silicate zeolite having the structure of ZSM-23, the admixture having hydrogenation/dehydrogenation activity to hydroisomerize the feedstock; and (b) passing at least a majority of the normally liquid hydrocarbon recovered from step (a) over a dewaxing catalyst comprising a crystalline silicate zeolite having a structure of ZSM-5, the zeolite of step (b) having hydrogenation/-dehydrogenation activity to dewax the recovered hydrocarbon.

  20. Cytokines and chemokines in neuromyelitis optica: pathogenetic and therapeutic implications.

    Science.gov (United States)

    Uzawa, Akiyuki; Mori, Masahiro; Masahiro, Mori; Kuwabara, Satoshi

    2014-01-01

    Neuromyelitis optica (NMO) is characterized by severe optic neuritis and longitudinally extensive transverse myelitis. The discovery of an NMO-specific autoantibody to the aquaporin-4 (AQP4) water channel has improved knowledge of NMO pathogenesis. Many studies have focused on inflammatory and pathological biomarkers of NMO, including cytokines and chemokines. Increased concentrations of T helper (Th)17- and Th2-related cytokines and chemokines may be essential factors for developing NMO inflammatory lesions. For example, interleukin-6 could play important roles in NMO pathogenesis, as it is involved in the survival of plasmablasts that produce anti-AQP4 antibody in peripheral circulation and in the enhancement of inflammation in the central nervous system. Therefore, assessment of these useful biomarkers may become a supportive criterion for diagnosing NMO. Significant advances in the understanding of NMO pathogenesis will lead to the development of novel treatment strategies. This review focuses on the current advances in NMO immunological research, particularly that of cytokines and chemokines.

  1. Chemokines in the corpus luteum: Implications of leukocyte chemotaxis

    Directory of Open Access Journals (Sweden)

    Liptak Amy R

    2003-11-01

    Full Text Available Abstract Chemokines are small molecular weight peptides responsible for adhesion, activation, and recruitment of leukocytes into tissues. Leukocytes are thought to influence follicular atresia, ovulation, and luteal function. Many studies in recent years have focused attention on the characterization of leukocyte populations within the ovary, the importance of leukocyte-ovarian cell interactions, and more recently, the mechanisms of ovarian leukocyte recruitment. Information about the role of chemokines and leukocyte trafficking (chemotaxis during ovarian function is important to understanding paracrine-autocrine relationships shared between reproductive and immune systems. Recent advances regarding chemokine expression and leukocyte accumulation within the ovulatory follicle and the corpus luteum are the subject of this mini-review.

  2. Early detection of neonatal group B streptococcus sepsis and the possible diagnostic utility of IL-6, IL-8, and CD11b in a human umbilical cord blood in vitro model

    Science.gov (United States)

    Nakstad, Britt; Sonerud, Tonje; Solevåg, Anne Lee

    2016-01-01

    Background Group B streptococcus (GBS) infection remains a major cause of neonatal morbidity and mortality, and GBS III is the predominant strain in early-onset GBS neonatal sepsis. To avoid both over- and undertreatment of infants with nonspecific signs of infection, early diagnostic tools are warranted. The aim of this study was to identify biomarkers with high sensitivity and specificity in an early stage of GBS infection. A secondary aim was to assess the utility of a human umbilical cord blood (HUCB) model system of early-onset neonatal sepsis. Methods Umbilical cord blood samples from 20 healthy term pregnancies were stimulated for 2 hours with a GBS III isolate from a patient and a commercially available GBS Ia strain. Nonstimulated samples served as controls. Leukocyte surface markers (CD11b, CD64, toll-like receptor [TLR] 2, TLR4, and TLR6) were analyzed by flow cytometry and soluble biomarkers by enzyme-linked immunosorbent assay (interleukin [IL]-6 and -8; interferon-γ-inducing protein [IP]-10; and S100b). The area under the receiver operating characteristic curve (AUC) was calculated for the markers. Results GBS III gave the highest responses and AUC values for all biomarkers. Only IL-6 and IL-8 displayed an AUC approaching 0.8 for both GBS serotypes (P5,292 pg/mL had both a sensitivity and a specificity of 1.00. IL-6 >197 pg/mL had both a sensitivity and a specificity of 0.95 for GBS III stimulation. CD11b on granulocytes and monocytes was the leukocyte surface marker with the highest AUC values for both GBS serotypes. Conclusion In agreement with previous studies, IL-6, IL-8, and potentially CD11b could be useful in diagnosing neonatal GBS infection in an early stage. Our HUCB early-onset neonatal sepsis model may be useful for evaluating biomarkers of neonatal sepsis. The HUCB of neonates with risk factors for sepsis might even be used for diagnostic purposes, but requires further study. PMID:27468243

  3. 肽聚糖对正常人表皮角质形成细胞分泌趋化因子的影响及Toll样受体2的作用%Peptidoglycan modulation of chemokine production in normal human epidermal kerafinocytes and the role of Toll-like receptor 2 in this process

    Institute of Scientific and Technical Information of China (English)

    刘苏俊; 林麟; 张彩萍; 周武庆; 冯雨苗; 马一平

    2009-01-01

    Objective To investigate the effect ofpeptidoglycan from Staphylococcus aureus on the release of several chemokines including intedeukin 8 (IL-8), regulated upon activation, normal T cell expressed and secreted (RANTES), macrophage-derived chemokine (MDC) by normal human epidermal keratinocytes (KCs) and the role of Toll-like receptor 2 (TLR2) in this process. Methods KCs were derived from the foreskin of a healthy boy and propagated. After 2 - 4 passages, KCs were collected and treated with various concentrations (3, 10, 30 and 100 mg/L) of peptidoglycan for 24 hours or with peptidoglycan of 100 mg/L for varying durations (3, 6, 12, 36 hours). A fi'action of KCs were pretreated with functional grade purified anti-TLR2 monoclonal antibody before the treatment with peptidoglycan of 100 mg/L. After additional 12-hour culture following the treatment, enzyme linked immunosorbent assay was used to detect the level of IL-8, RANTES and MDC in culture supernatants of KCs. Results KCs spontaneously released IL-8 and RANTES. Peptidoglycan increased the production of IL-8 but decreased that of RANTES by KCs. The levels of IL-8 were 209.96 ± 10.31 ng/L, 250.28 ± 9.52 ng/L, 285.11 ± 10.28 ng/L, 359.40 ± 6.93 ng/L in KCs treated with peptidoglycan of 3, 10, 30, 100 mg/L, respectively, compared to 135.41 ± 14.37 ng/L in untreated KCs (all P < 0.05). On the contrary, a significant decrement was seen in the secretion of RANTES by KCs treated with peptidoglycan of 10, 30, 100 mg/L compared with untreated KCs (110.72 ± 8.51 ng/L, 90.50 ±2.45 ng/L, 49.89 ± 13.74 ng/L vs 149.94 ± 18.71 ng/L, all P < 0.05). The monoclonal antibody to TLR-2 could markedly suppress the promotion of IL-8 production by peptidoglycan, but had no obvious influence on the inhibition of RANTES production by peptidoglycan. MDC could not be detected in the culture super-natants of KCs with or without peptidoglycan stimulation. Conclusion Peptidoglycan could inhibit RANTES secretion but induce IL-8

  4. Energy Cascades in MHD

    Science.gov (United States)

    Alexakis, A.

    2009-04-01

    Most astrophysical and planetary systems e.g., solar convection and stellar winds, are in a turbulent state and coupled to magnetic fields. Understanding and quantifying the statistical properties of magneto-hydro-dynamic (MHD) turbulence is crucial to explain the involved physical processes. Although the phenomenological theory of hydro-dynamic (HD) turbulence has been verified up to small corrections, a similar statement cannot be made for MHD turbulence. Since the phenomenological description of Hydrodynamic turbulence by Kolmogorov in 1941 there have been many attempts to derive a similar description for turbulence in conducting fluids (i.e Magneto-Hydrodynamic turbulence). However such a description is going to be based inevitably on strong assumptions (typically borrowed from hydrodynamics) that do not however necessarily apply to the MHD case. In this talk I will discuss some of the properties and differences of the energy and helicity cascades in turbulent MHD and HD flows. The investigation is going to be based on the analysis of direct numerical simulations. The cascades in MHD turbulence appear to be a more non-local process (in scale space) than in Hydrodynamics. Some implications of these results to turbulent modeling will be discussed

  5. Generating substrate bound functional chemokine gradients in vitro

    DEFF Research Database (Denmark)

    Hjortø, Gertrud Malene; Hansen, Morten; Larsen, Niels Bent;

    2009-01-01

    Microcontact printing (mCP) is employed to generate discontinuous microscale gradients of active fractalkine, a chemokine expressed by endothelial cells near sites of inflammation where it is believed to form concentration gradients descending away from the inflamed area. In vivo, fractalkine...... is a transmembrane molecule extending its chemokine domain into the vascular lumen. Substrate bound in vitro gradients may thus closely resemble in vivo conditions. Direct mCP of sensitive proteins like fractalkine may cause partial protein denaturation and will not ensure correct orientation of the biologically...

  6. Discovery of indole inhibitors of chemokine receptor 9 (CCR9).

    Science.gov (United States)

    Pandya, Bhaumik A; Baber, Christian; Chan, Audrey; Chamberlain, Brian; Chandonnet, Haoqun; Goss, Jennifer; Hopper, Timothy; Lippa, Blaise; Poutsiaka, Katherine; Romero, Jan; Stucka, Sabrina; Varoglu, Mustafa; Zhang, Jing; Zhang, Xin

    2016-07-15

    Irritable bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC) are serious chronic diseases affecting millions of patients worldwide. Studies of human chemokine biology has suggested C-C chemokine receptor 9 (CCR9) may be a key mediator of pro-inflammatory signaling. Discovery of agents that inhibit CCR9 may lead to new therapies for CD and UC patients. Herein we describe the evolution of a high content screening hit (1) into potent inhibitors of CCR9, such as azaindole 12. PMID:27256913

  7. The Effects of Ulinastatin on Oxygen Free Radical and IL-6、IL-8、TNF-a During One Lung Ventilation after Chemotherapy to Patients with Lung Cancer%化疗后肺癌病人单肺通气时氧自由基、IL-6、IL-8和TNF-α的变化和乌司他丁的保护作用

    Institute of Scientific and Technical Information of China (English)

    马武华; 吴一龙; 李朝霞

    2004-01-01

    目的探讨化疗后肺癌病人单肺通气时氧自由基、IL-6、IL-8和TNF-α的变化和乌司他丁的保护作用.方法择期行肺癌手术病人30例,按美国麻醉医师协会(ASA)分级为Ⅱ~Ⅲ级;随机分为乌司他丁组(U组)和对照组(C组),每组各15例.U组给予乌司他丁1万U·kg-1,于麻醉诱导后缓慢静注,C组用等量生理盐水代替.分别于麻醉诱导后(S1)、单肺通气40min(S2)、单肺通气90min(S3)、术毕双肺通气30min(S4)、术后24h(S5)采集外周静脉血样测SOD、MDA、IL-6、IL-8和TNF-α.结果 C组SOD在S3、S4时明显降低(P<0.05),U组从S2开始升高,且U组在S3、S4时均明显高于C组(P<0.05);两组MDA于S3、S4时均显著升高(P<0.05),但两组之间无明显差别.两组IL-6于S2后均显著升高(P<0.05),和C组比较,U组S3、S4时均显著降低(P<0.05).两组IL-8于S3、S4、S5时均显著升高(P<0.05),和C组比较,U组S3、S4时均显著降低(P<0.05).两组TNF-α于S2、S3、S4时均显著升高(P<0.05),和C组比较,U组S3时均显著降低(P<0.05).结论乌司他丁可减轻化疗后病人单肺通气期间炎性因子的生成和释放,减少氧自由基的产生,从而减轻病人的炎症反应.

  8. Dual GPCR and GAG mimicry by the M3 chemokine decoy receptor

    Energy Technology Data Exchange (ETDEWEB)

    Alexander-Brett, Jennifer M.; Fremont, Daved H. (WU-MED)

    2008-09-23

    Viruses have evolved a myriad of evasion strategies focused on undermining chemokine-mediated immune surveillance, exemplified by the mouse {gamma}-herpesvirus 68 M3 decoy receptor. Crystal structures of M3 in complex with C chemokine ligand 1/lymphotactin and CC chemokine ligand 2/monocyte chemoattractant protein 1 reveal that invariant chemokine features associated with G protein-coupled receptor binding are primarily recognized by the decoy C-terminal domain, whereas the N-terminal domain (NTD) reconfigures to engage divergent basic residue clusters on the surface of chemokines. Favorable electrostatic forces dramatically enhance the association kinetics of chemokine binding by M3, with a primary role ascribed to acidic NTD regions that effectively mimic glycosaminoglycan interactions. Thus, M3 employs two distinct mechanisms of chemical imitation to potently sequester chemokines, thereby inhibiting chemokine receptor binding events as well as the formation of chemotactic gradients necessary for directed leukocyte trafficking.

  9. IFN-gamma shapes immune invasion of the central nervous system via regulation of chemokines

    DEFF Research Database (Denmark)

    Tran, E H; Prince, E N; Owens, T

    2000-01-01

    Dynamic interplay between cytokines and chemokines directs trafficking of leukocyte subpopulations to tissues in autoimmune inflammation. We have examined the role of IFN-gamma in directing chemokine production and leukocyte infiltration to the CNS in experimental autoimmune encephalomyelitis (EA...

  10. Expression of toll-like receptors by human muscle cells in vitro and in vivo: TLR3 is highly expressed in inflammatory and HIV myopathies, mediates IL-8 release and up-regulation of NKG2D-ligands.

    Science.gov (United States)

    Schreiner, Bettina; Voss, Joachim; Wischhusen, Jörg; Dombrowski, Yvonne; Steinle, Alexander; Lochmüller, Hanns; Dalakas, Marinos; Melms, Arthur; Wiendl, Heinz

    2006-01-01

    The particular microenvironment of the skeletal muscle can be the site of complex immune reactions. Toll-like receptors (TLRs) mediate inflammatory stimuli from pathogens and endogenous danger signals and link the innate and adaptive immune system. We investigated innate immune responses in human muscle. Analyzing TLR1-9 mRNA in cultured myoblasts and rhabdomyosarcoma cells, we found constitutive expression of TLR3. The TLR3 ligand Poly (I:C), a synthetic analog of dsRNA, and IFN-gamma increased TLR3 levels. TLR3 was mainly localized intracellularly and regulated at the protein level. Poly (I:C) challenge 1) activated nuclear factor-kappaB (NF-kappaB), 2) increased IL-8 release, and 3) up-regulated NKG2D ligands and NK-cell-mediated lysis of muscle cells. We examined muscle biopsy specimens of 6 HIV patients with inclusion body myositis/polymyositis (IBM/PM), 7 cases of sporadic IBM and 9 nonmyopathic controls for TLR3 expression. TLR3 mRNA levels were elevated in biopsy specimens from patients with IBM and HIV-myopathies. Muscle fibers in inflammatory myopathies expressed TLR3 in close proximity of infiltrating mononuclear cells. Taken together, our study suggests an important role of TLR3 in the immunobiology of muscle, and has substantial implications for the understanding of the pathogenesis of inflammatory myopathies or therapeutic interventions like vaccinations or gene transfer.

  11. 齿龈阿米巴感染对牙周炎患者血清TNF-α、IL-1β、IL-8和NO水平的影响

    Institute of Scientific and Technical Information of China (English)

    李继红; 李小丹

    2005-01-01

    牙周炎是由牙菌斑中的细菌特别是G厌氧菌混合感染引起的,有文献认为:在某些人群中(其中)约有65%的牙周炎合并齿龈内阿米巴(Entamoeba ginfivalis,Eg)感染。不少学者对牙周炎时局部组织和分泌物中肿瘤坏死因子α(TNF—α)、白细胞介素-1β(IL-1β)、白细胞介素-8(IL-8)和一氧化氮(NO)的含量及表达进行了详细检测,但很少涉及这些因子的血清水平。为了了解细菌和细菌合并Eg感染时这些因子的血清水平,作者对40例牙周炎患者(20例合并Eg感染)和健康志愿者进行了检测。现将检测结果报告如下:

  12. 白细胞介素4、白细胞介素8、白细胞介素10在哮喘和慢性阻塞性肺疾病发病中的作用%Role of IL-4, IL-8 and IL-10 in Asthma and Chronic Obstructive Pulmonary Disease

    Institute of Scientific and Technical Information of China (English)

    崔丽英; 任卉; 郝璐; 高春桃

    2012-01-01

    Objective:Thc research aims at studying the role of peripheral blood intcricukin 4 (IL-4) , intcricukin 8 (IL-8) and intcricukin 10 (IL-10) in asthma and chronic obstructive pulmonary disease (COPD). Methods: Use double-antibody sandwich enzyme-linked immunosorbent assam (ELISA) to detect the content of scrum IL-4, IL-8 and IL-10 in 50 cases of acute exacerbation of COPD (AECOPD) , 50 cases of paracmastic COPD, 50 cases of acute asthma, 50 cases of paracmastic asthma and 50 cases of healthy volunteers (healthy control group). Results: The levels of IL-4 and IL-8 in the scrum of the patients with acute asthma were significantly higher than that of the paracmastic asthma group(P<0. 01) , while the levels of scrum IL-4,IL-8 in these two groups were significantly higher than that in the healthy group (PIL-8 in the scrum of the patients with AECOPD was significantly higher than that in the paracmastic COPD group(P<0. 01) , while the levels of scrum IL-4 and IL-8 in the two groups were significantly higher than that in the healthy group (P< 0. 01). The IL-10 level in the scrum of the patients with AECOPD was significantly lower than that of the paracmastic COPD group(P<0. 01) and the levels of scrum IL-10 in both groups were singnificantly lower than in the healthy group (PIL-8 level in AECOPD was significantly higher than in the acute asthma group (PIL-8 and IL-10 arc engaged in asthma and COPD airway inflammatory

  13. Expressions of serum IL-8 and COX-2 in triple negative breast cancer patients and clinical significance%三阴性乳腺癌患者血清白细胞介素8和环氧化酶2的含量及临床意义

    Institute of Scientific and Technical Information of China (English)

    李庆; 陈守华; 顾禾; 张丽丽

    2010-01-01

    目的 探讨三阴性乳腺癌患者手术前、后血清白细胞介素8(IL-8)、环氧化酶2(COX-2)表达变化及临床意义.方法 采用酶联免疫吸附测定-双抗体夹心法(enzyme linked immunosorbent assay sandwich technique,ELISA)检测手术前、后72例乳腺癌患者(乳腺癌组)和54例良性乳腺肿物患者(对照组)血清IL-8、COX-2的表达.血清IL-8、COX-2含量在两组间比较采用t检验.术前与术后比较和术后与术后1年比较采用配对t 检验.结果 手术前乳腺癌组血清IL-8、COX-2表达明显高于对照组(P 值均是0.000).手术后乳腺癌组与对照组比较血清IL-8、COX-2表达差异均无统计学意义(P>0.050).乳腺癌组手术前血清IL-8、COX-2表达明显高于手术后(P 值均是0.000).72例乳腺癌患者中术后1年内复发4例;4例复发患者术后和术后1年血清IL-8、COX-2水平均高于无复发患者(P 值均<0.050).结论 乳腺癌患者手术前、后IL-8和COX-2水平变化显著,可能对判断治疗效果有一定的参考意义.

  14. Cascade Error Projection Learning Algorithm

    Science.gov (United States)

    Duong, T. A.; Stubberud, A. R.; Daud, T.

    1995-01-01

    A detailed mathematical analysis is presented for a new learning algorithm termed cascade error projection (CEP) and a general learning frame work. This frame work can be used to obtain the cascade correlation learning algorithm by choosing a particular set of parameters.

  15. The emerging role of CXC chemokines and their receptors in cancer.

    Science.gov (United States)

    Vinader, Victoria; Afarinkia, Kamyar

    2012-05-01

    Chemokines and their receptors have a multifaceted role in tumor biology and are implicated in nearly all aspects of cancer growth, survival and dissemination. Modulation of the interaction between chemokines and their cell surface receptor is, therefore, a promising area for the development of new cancer medicines. In this review, we look at the compelling evidence that is emerging to support targeting CXC chemokines, also known as family α chemokines, as novel therapeutic strategies in the treatment of cancer. PMID:22571611